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Resolution of cardiomyopathy after ablation of atrial flutter.

OBJECTIVES: We sought to serially assess left ventricular (LV) function before and after catheter ablation of atrial flutter (AFI). BACKGROUND: The relation of tachycardia-induced cardiomyopathy to AFI and its response to direct catheter ablation are unknown. METHODS: LV function was assessed in a series of 59 consecutive patients with successful radiofrequency ablation (RFA) of AFI before and after the procedure. Eleven patients had dilated cardiomyopathy (LV ejection fraction [LVEF] <50%) and congestive heart failure (CHF) symptoms and are the subject of this report. LV function was assessed by LVEF on two-dimensional echocardiography and functional status by New York Heart Association (NYHA) CHF classification. RESULTS: Patients were 59 +/- 8 years old, and were all male. Five patients had a preablation diagnosis of idiopathic cardiomyopathy. The preablation LVEF was 30.9 +/- 11.0% and improved to 41.3 +/- 16% (p = 0.005) when measured 7 months after successful ablation. NYHA CHF class improved from 2.6 +/- 0.5 to 1.6 +/- 0.9 (p = 0.002). Six (55%) of 11 patients had normalization of the LVEF, with complete resolution of CHF symptoms. A lower preablation LVEF and functional class predicted nonresolution of dilated cardiomyopathy (p = 0.002 and 0.001, respectively). CONCLUSIONS: Restoration of normal sinus rhythm by RFA in patients with chronic AFI and cardiomyopathy substantially improved LV function. Resolution of dilated cardiomyopathy occurred in the majority of patients. Tachycardia-induced cardiomyopathy may be a more common mechanism of LV dysfunction in patients with AFI than expected, and aggressive treatment of this arrhythmia should be considered.

Adult↗

Impaired cardiac adjustment to pregnancy in type I diabetes.

To assess the adaptation of the heart of diabetic subjects in the natural volume overload state of pregnancy, echocardiography was performed during each trimester and postpartum in 17 women with insulin-dependent diabetes mellitus (IDDM) and in 11 healthy women. The mean duration of diabetes was 14 yr and signs of microvascular complications were detected in 6 patients. The diabetic women had slightly smaller left ventricles than the control women already in the basal state (postpartum), and the pregnancy-induced increase in left ventricular size and stroke volume was less in the diabetic than in the control women. The heart rate rise also tended to be less in the diabetic women, resulting in a markedly smaller increase in cardiac output in this group (1.3 vs. 3.4 L/min, P less than .01). Left ventricular systolic function, wall thicknesses, or left atrial size did not differ between the groups at any point in the study. Minor collections of pericardial fluid were observed in 14 (76%) diabetic women and in 5 (45%) control women during the second and/or third trimester, but only 2 diabetic women had classic pericardial effusions. In conclusion, the normal hemodynamic adjustments to pregnancy seem to be impaired in women with IDDM. Preclinical diabetic cardiomyopathy and autonomic neuropathy may be involved in the observed alterations.

Adult↗

Flecainide versus ibutilide for immediate cardioversion of atrial fibrillation of recent onset.

AIMS: This study compared the efficacy and safety of intravenous flecainide and ibutilide for immediate cardioversion of atrial fibrillation (AF). METHODS AND RESULTS: We conducted a prospective, randomised trial, including 207 patients with AF of recent onset (< or = 48 h). Flecainide was given over 20 min at a dose of 2 mg/kg body weight (maximum 200 mg), ibutilide was infused at a dose of 1 mg (or 0.01 mg/kg if less than 60 kg) over 10 min, followed by a 10 min observation period and an identical second dose if AF did not convert to sinus rhythm (SR). Treatment was considered successful if SR occurred within 90 min of starting medication. The conversion rates were 56.4% in patients given flecainide and 50.0% in patients given ibutilide (P=0.34). Multivariate analysis revealed that a lower age for women independently increased the probability of conversion. None of the other variables, including left atrial size, left ventricular systolic function, presence of left ventricular hypertrophy, plasma levels of potassium or magnesium at baseline, or concomitant use of digoxin, beta-blocker, diltiazem or verapamil were predictors of conversion. The frequency of adverse events was comparable in the two treatment groups. CONCLUSIONS: There was no significant difference in the cardioversion efficacy or in the risk of adverse events between flecainide and ibutilide in patients with AF of recent onset. In patients without contraindications to both medications, the physician's choice has to be governed by other factors.

Anti-Arrhythmia Agents↗

Echocardiographic parameters in reversible idiopathic dilated cardiomyopathy.

BACKGROUND: Reversible idiopathic dilated cardiomyopathy (IDCM) is a rare entity. It has been hypothesized that the degree of left ventricular end diastolic dilation is an important independent predictor of prognosis. We undertook a study to identify cases of reversible IDCM and to evaluate the echocardiographic findings in these patients. METHODS: We identified 5 patients with IDCM who showed normalization of left ventricular function over a follow up period of 5 months. The findings were compared with those of 10 patients with IDCM who did not show improvement of left ventricular function. The mean (+/-SE) left atrial and left ventricular (LV) dimensions and ejection fraction at baseline and follow-up were compared in both groups. RESULTS: There were no statistical differences between the mean (+/-SE) left atrium sizes in the cases and control group at baseline [4.52 (+/-0.24) cm v4.6 (+/-0.13) cm; P = 0.758]. Also, no differences were observed between mean (+/-SE) LV dimensions in diastole and systole in both groups at baseline [LV diastole, 6.72 (+/-0.35) cm versus 6.56 (+/-0.22) cm; P = 0.711; LV systole, 5.6 (+/-0.27) cm versus 5.59 (+/-0.29) cm; P = 0.712] as well as in mean (+/-SE) ejection fraction [24% (+/-3.96) versus 21.7% (+/-3.30); P = 0.623]. CONCLUSION: Based on initial echocardiographic parameters, chamber dimensions and baseline LV ejection fraction are not predictors of reversibility.

Adult↗

Online Quantification of Cardiovascular Function in Children.

Echocardiography is the most valuable diagnostic tool in evaluating congenital anatomic pathology. Improvements in transducer resolution and development of color Doppler echocardiography have resulted in the ability to delineate cardiac anatomy in detail. Online quantification of cardiovascular function represents a similar advance in terms of evaluating physiology. Performing an online quantification examination requires attention to technical factors such as avoiding chamber foreshortening, optimizing endocardial tracking, ensuring patient cooperation, and accounting for the effects of respiration. A typical examination consists of performing acoustic quantification on the left ventricle in both short-axis and apical four-chamber views and on the left atrium from the apical four-chamber view. From these views, ventricular systolic and diastolic function, as well as atrial systolic function, can be assessed. As in adult patients, acoustic quantification indices in children correlate well with similar indices measured off line. Acoustic quantification data in children show that, unlike adults, the left ventricular filling is almost exclusively dependent on passive filling, with minimal atrial contribution. Acoustic quantification indices have also been useful in monitoring left ventricular function in intensive care and emergency department settings to evaluate the acute effects of a clinical manipulation. Acoustic quantification can also be used to assess the function of ventricles of unusual geometry such as in hypoplastic left and right heart, double-inlet single ventricle, and unbalanced atrial ventricular septal defect. In these types of ventricles, systolic and diastolic systemic ventricular function has been shown to be markedly altered compared with a normal left ventricle. Acoustic quantification can also be used to assess diastolic function in a variety of pediatric diseases, such as transplant rejection and insulin-dependent diabetes mellitus. In summary, online quantification of cardiovascular function represents a significant advance in the ability to understand cardiovascular physiology in children.

Journal Article↗

Fetal lamb ventricles respond differently to filling and arterial pressures and to in utero ventilation.

Right and left ventricular function were investigated in 12 fetal lambs (127-140 days gestation) instrumented with electromagnetic flow sensors on the ascending aorta and the main pulmonary artery, and with vascular catheters. Nine fetuses were equipped with a postductal aortic occluder and the trachea was cannulated in eight. Control arterial blood values were pH 7.36 +/- 0.02 (SD), PCO2 49.3 +/- 2.3 torr, PO2 18.4 +/- 1.7 torr, and hematocrit 37.3 +/- 4.4%. Biventricular function curves relating stroke volume to mean right and left atrial pressure were generated by rapid withdrawal and reinfusion of fetal blood. Both function curves were composed of steep ascending and plateau limbs that intersected at a breakpoint. Stroke volumes at the breakpoints were 0.94 +/- 0.19 ml.kg-1 and 0.63 +/- 0.15 ml.kg-1 for right and left ventricle, respectively (p less than 0.001). During postductal aortic occlusion, arterial pressure increased by 19.3 +/- 7.9 torr while right ventricular stroke volume decreased by approximately 48% and left ventricular stroke volume decreased by approximately 9%. In utero ventilation increased arterial pressure, heart rate, PO2, and oxygen content. Right atrial pressure increased from 3.9 +/- 1.3 to 5.8 +/- 2.9 torr (p less than 0.05); left atrial pressure from 3.5 +/- 1.5 to 10.0 +/- 4.4 torr (p less than 0.05). Aortic flow nearly doubled (112 +/- 29 to 211 +/- 35 ml.min-1.kg-1) (p less than 0.05), and the left ventricular function curve shifted upward. The right ventricular function curve was shifted downward during ventilation. We conclude that the fetal ventricles differ significantly in their outputs, response to changes in arterial pressure, and to the onset of in utero ventilation.

Animals↗

Valve replacement in rheumatic mitral incompetence: total versus posterior chordal preservation.

Several studies have shown that mitral valve replacement with total chordal preservation (MVR-TCP) improves left ventricular function when compared with total chordal transection. Few clinical studies, however, have compared this technique to that involving only posterior chordal preservation (MVR-PCP). This study was intended to cover this aspect. A total of 36 consecutive patients with chronic rheumatic mitral incompetence were operated upon by one surgeon and benefited from MVR-TCP (group I). During the same period and along similar selection criteria, 60 patients underwent MVR-PCP (group II) in our department. With the exception of a statistically significant higher preoperative left ventricular ejection fraction (LVEF) percentage and lower fractional shortening (LVFS) percentage in group II patients; both groups were comparable as regarding age, sex distribution New York Heart Association (NYHA) functional class (FC), preoperative left atrial diameter (LAD), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) as well as aortic cross-clamp and cardiopulmonary bypass times. The means of the differences, between the pre- and postoperative values of NYHA FC and echocardiographic data were compared between both groups. As compared with group II, group I patients showed lower: hospital mortality rate (0 versus 8.3%; P > 0.05); need for positive inotropic support (11.1 versus 20.8%; P > 0.05) and total ICU stay (2.9 +/- 0.17 versus 2.2 +/- 0.13 days; P < 0.01). In addition, group I patients showed a better NYHA FC improvement (-2.08 +/- 0.15 versus -1.93 +/- 0.11; P > 0.05) as well as a statistically significant (P < 0.00001) higher decrease in the LAD (-18.19 +/- 0.97 versus -11.59 +/- 0.58 mm), LVEDD (-14.44 +/- 0.91 versus -6.17 +/- 0.05 mm), LVESD (-6.17 +/- 0.77 versus -3.23 +/- 0.01 mm), LVFS percentage (-0.06 +/- 0.01 versus -0.01 +/- 0.001%) and a higher increase in the LVEF percentage (8.1 +/- 0.9 versus 1.48 +/- 0.02%). The smaller mean diameter of the implanted St Jude prosthesis, in group I patients (26.77 +/- 0.22 versus 27.43 +/- 0.21 mm; P = 0.046), was neither associated with the use of a smaller prosthesis than that predicted for the patient size nor a significantly higher mean transprosthetic pressure gradient. These data suggest that in rheumatic patients with chronic mitral incompetence, MVR-TCP is always feasible: it is associated with lower hospital mortality and morbidity rates and better preservation of the postoperative left ventricular systolic functions when compared with MVR-PCP.

Adult↗

Interference of mitral valve stenosis with left ventricular diastole and left atrial appendage flow.

Atrial fibrillation (AF) has been reported as an independent risk factor of systemic thromboembolism. Almost half of the left atrial thrombi are located in the left atrial appendage (LAA). LAA function, reflected by LAA flow, thus has an influence on the potential of distal embolic complications. To identify factors other than atrial contraction that influence LAA flow during AF, transthoracic and transesophageal echocardiographic studies were performed on 130 patients. Seventy patients with nonrheumatic AF were divided into two groups with higher peak LAA outflow velocity (group 1) and lower peak LAA outflow velocity (group 2) at the ventricular systolic phase. Sixty patients with rheumatic AF were classified as group 3. Group 1 had a higher peak LAA outflow velocity than group 2 at both the ventricular systolic and diastolic phases. Group 2 had a higher peak LAA outflow at the ventricular diastolic phase than group 3 (18.9 +/- 8.0 vs. 11.8 +/- 7.5 cm/s, p < 0.001), whereas there was no significant difference in the peak LAA outflow at the ventricular systolic phase between the two groups (9.6 +/- 4.0 vs. 10.8 +/- 6.8 cm/s, p = NS). Group 3 was subdivided according to mitral valve area. Patients with severe mitral stenosis (mitral valve area < 1 cm2) had a significantly lower diastolic augmentation of LAA outflow velocity (difference of LAA outflow velocity between ventricle systole and diastole) than patients with mild to moderate stenosis (0.5 +/- 3.2 vs. 2.6 +/- 4.9 cm/s, p < 0.05). In conclusion, patients with rheumatic AF, especially those with severe mitral stenosis, have a lower diastolic augmentation of LAA outflow velocity. The lower diastolic augmentation of the LAA outflow velocity at the ventricular diastolic phase might result from interference with the suction effect of the left ventricular diastole by the stenotic mitral valve.

Aged↗

Efficacy and safety of intravenous amiodarone in recent-onset atrial fibrillation: experience in patients admitted to a general internal medicine department.

We examined the efficacy and safety of intravenous amiodarone in 20 unselected patients with recent-onset atrial fibrillation who were admitted to a general internal medicine department during a 6-month period. The treatment protocol included a loading dose of 1200 mg intravenous amiodarone in 24 hours, after which amiodarone treatment was continued orally. Eleven of the 20 patients (55%) converted to sinus rhythm within 48 hours of intravenous amiodarone treatment and were discharged in sinus rhythm, while 9/20 (45%) patients failed to convert during hospitalisation. Six patients (30%) failed to convert to sinus rhythm even after one further month of oral treatment. There was one death and a high frequency (25%) of thrombophlebitis during hospitalisation. The in-hospital non-convertors had a significantly lower ejection fraction and initial low ventricular response rate than the convertors. In conclusion, the acute conversion rate by intravenous amiodarone was at best modest. It is suggested that intravenous amiodarone is probably more effective in patients with rapid recent-onset atrial fibrillation and good left ventricular function.

Aged↗

Atrial septal pacing to synchronize atrial depolarization in patients with delayed interatrial conduction.

The current method of pacing the right atrium from the appendage or free wall is often the source of delayed intraatrial conduction and discoordinate left and right atrial mechanical function. Simultaneous activation of both atria with pacing techniques involving multisite and multilead systems is associated with suppression of supraventricular tachyarrhythmias and improved hemodynamics. In the present study we tested the hypothesis that pacing from a single site of the atrial septum can synchronize atrial depolarization. Five males and two females (mean age 58 +/- 6 years) with drug refractory paroxysmal atrial fibrillation (AF) were studied who were candidates for AV junctional ablation. All patients had broad P waves (118 +/- 10 ms) on the surface ECG. Multipolar catheters were inserted and the electrograms from the high right atrium (HRA) and proximal, middle, and distal coronary sinus (CS) were recorded. The atrial septum was paced from multiple sites. The site of atrial septum where the timing between HRA and distal CS (d-CS) was < or = 10 ms was considered the most suitable for simultaneous atrial activation. An active fixation atrial lead was positioned at this site and a standard lead was placed in the ventricle. The interatrial conduction time during sinus rhythm and AAT pacing and the conduction time from the pacing site to the HRA and d-Cs during septal pacing were measured. Atrial septal pacing was successful in all patients at sites superior to the CS o.s. near the fossa ovalis. During septal pacing the P waves were inverted in the inferior leads with shortened duration from 118 +/- 10 ms to 93 +/- 7 ms (P < 0.001), and the conduction time from the pacing site to the HRA and d-CS was 54.3 +/- 6.8 ms and 52.8 +/- 2.5 ms, respectively. The interatrial conduction time during AAT pacing was shortened in comparison to sinus rhythm (115 +/- 18.9 ms vs 97.8 +/- 10.3 ms, P < 0.05). In conclusion, simultaneous activation of both atria in patients with prolonged interatrial conduction time can be accomplished by pacing a single site in the atrial septum using a standard active fixation lead placed under electrophysiological study guidance. Such a pacing system allows proper left AV timing and may prove efficacious in preventing various supraventricular tachyarrhythmias.

Atrial Fibrillation↗

Diastolic dysfunction in patients with non-insulin-dependent diabetes mellitus of short duration.

To determine whether abnormal left ventricular diastolic function is present at an early stage of non-insulin-dependent diabetes mellitus (NIDDM), left ventricular diastolic filling was evaluated by pulsed doppler echocardiography in 16 normotensive patients with NIDDM of short duration (1.8 +/- 1 years, mean +/- SD) and no evidence of microangiopathy, and in 16 healthy volunteers comparable for age, body mass index, and sex distribution. All patients showed normal systolic function. The interventricular septum thickness, left atrial diameter, and left ventricular mass index were increased in the diabetic as compared with the control group (p < 0.01, p < 0.01, and p < 0.02, respectively). Isovolumic relaxation time and atrial peak filling velocity were greater in diabetic patients (p < 0.001, and p < 0.01, respectively), whereas early to atrial peak filling velocity ratio was significantly reduced (p < 0.05). This study demonstrates that an impairment of left ventricular diastolic function occurs early in the natural history of NIDDM, and that this abnormality is unlikely to be related to clinical evidence of microangiopathic complications.

Acute Disease↗

Left atrial volume estimation by two-dimensional echocardiography.

We examined 12 patients aged six months to 76 years by echocardiography to determine left atrial volume. The results were compared with angiographic left atrial volumes calculated by the biplane Simpson's rule method. Three two-dimensional planes were used: precordial long axis, apical two-chamber, and four-chamber. Area outlines were traced using a light pen computational system providing single plane area length estimates of left atrial volume. The two apical left atrial outlines were combined, and Simpson's rule method was used to calculate left atrial volume. M-mode echocardiograms performed on these patients were used to estimate left atrial volume. As the results of covariance analysis showed that there was no significant difference in the line of regression in systole and diastole, these data were pooled for subsequent comparison with angiography. The closest correlation with angiography was the biplane Simpson rule method with the echocardiographic left atrial volume (Y) = 1.0, angiographic volume (X) + 6.3 ml, r = 0.86. The single plane area length estimates also correlated well with angiography, but correction factors were required. M-mode estimates of left atrial volume could only correlate to angiography using a power function y = 3.7 X(1.80), r = 0.69. We conclude that left atrial volume can be determined by two-dimensional echocardiography and that this technique is superior to M-mode echocardiography.

Adolescent↗

Combined radiofrequency modified maze and mitral valve procedure through a port access approach: early and mid-term results.

OBJECTIVE: The aim of this study was to assess the feasibility and effectiveness of irrigated radiofrequency (RF) modified Maze procedure through a port access approach during mitral valve surgery and evaluate early and mid-term results. MATERIAL AND METHOD: During a 16 months time period, 67 patients with chronic atrial fibrillation (AF) eligible for port access mitral valve surgery were randomly assigned to either Group A, in which they underwent a combined procedure (N = 33) or Group B, in which a valve procedure alone was performed (N = 34). Both groups were similar in terms of age, sex, valve pathology, duration of AF left atrial diameter and left ventricle function (P > 0.05). Four had undergone previous operations. RESULTS: Median follow-up was 10 months for both groups, 95% CI (9.18-10.8). One patient in each group died early postoperatively (3 and 2.9%). Two patients required reoperation for bleeding, one in each group (3 and 2.9%). There were two conversions to right thoracotomy. In Group A, freedom from AF was 100% at the end of the operation (76% sinus, 24% pacemaker) Six and twelve months freedom from AF was 87.2 and 93.6%, respectively. In Group B, freedom from AF at the end of operation was 41%. At the end of 6 and 12 months, freedom from AF was 9.4% (P = 0.0001). One patient in Group A required a permanent pacemaker (3%). During follow-up, one patient in Group A died of non-cardiac causes (3%). In Group B, there were two late deaths: one cardiac (2.9%) and one neurologic (2.9%). There were no thromboembolic events detected in Group A during follow-up, whereas two patients in Group B suffered this complication (6%, P = 0.081). At 12 months, functional capacity had improved for patients in both groups (P < 0.0001). CONCLUSION: The combination of mitral valve surgery and irrigated RF Maze procedure was safe and efficient through a port access approach. There were no procedure related complications like esophageal or coronary artery injury. Early and mid-term results were favourable with 93.6% of patients free of AF at 1 year in comparison to the 9.4% of the control group. The data is not sufficient to reach any conclusions in terms of thromboembolic rates, despite favourable results for the RF Maze group. Nevertheless, in terms of feasibilty, sinus rhythm restoration and overall outcome, early results are encouraging and we advocate the use of the combined procedure through a port access approach.

Adult↗

Left ventricular performance during acute rate control in atrial fibrillation: the importance of heart rate and agent used.

BACKGROUND: The relation between heart rate and left ventricular function during rate control in atrial fibrillation is incompletely understood. METHODS: Twenty-four patients (age 67 +/- 11 years) with symptomatic recent onset rapid atrial fibrillation and rapid ventricular rate (> 110 bpm) were randomly assigned to receive either intravenous digoxin (13 mcg/kg) or intravenous diltiazem (0.25 mg/kg bolus plus a maintenance infusion). A portable radionuclide detector was used to collect validated measures of relative left ventricular volumes, along with heart rate data, every 15 seconds for 6 hours. RESULTS: Heart rate decreased significantly at 15 minutes and 180 minutes in the diltiazem group (from 133 +/- 18 bpm to 111 +/- 26 bpm [P <.01] to 94 +/- 24 bpm [P <.001]) but not in the digoxin group (from 129 +/- 18 bpm to 126 +/- 17 bpm [P = NS] to 118 +/- 15 bpm [P = NS]). Left ventricular ejection fraction improved in both groups to a similar extent (from 39 +/- 10% to 50 +/- 8%, [P <.05] after diltiazem, and from 38 +/- 8% to 52 +/- 11% [P <.05] after digoxin at baseline vs 180 minutes, respectively). The ejection fraction vs heart rate slope was steeper in the digoxin group than in the diltiazem group (-0.34 +/- 0.18 vs -0.16 +/- 0.17, P =.048) indicating a more pronounced improvement in ejection fraction per unit decrease in heart rate. CONCLUSION: In patients with acute atrial fibrillation, digoxin led to similar improvements in ejection fraction compared to diltiazem despite a slower and less potent heart rate slowing.

Aged↗

Percutaneous balloon mitral valvuloplasty. An observation of 50 patients.

Percutaneous balloon mitral valvuloplasty (PBMV) was successfully performed in 50 selected patients with mitral stenosis by using Inoue pillow-shaped balloon and Inoue technique. The average diameter of balloon used was 26.9 +/- 0.9 mm. 90% (45/50) of cases had either double or single mitral commissura split. Of the rest 5 cases, 1 had a mitral score 13 and 4 had a history of mitral valve commissurotomy. Totally they had a mean mitral valve area increase from 1.13 +/- 0.32 to 2.21 +/- 0.43 cm2, left atrial pressure decrease from 31.8 +/- 9.3 to 14.7 +/- 5.6 mmHg, left atrial diameter reduction from 44.9 +/- 7.7 to 37.4 +/- 4.9 mm, and transmitral gradient decrease from 21.7 +/- 9.8 to 4.0 +/- 5.2 mmHg. Most patients had a obvious cardiac function improvement, especially in patients with mitral score of 8 or less. 30% patients (15/50) had a mild mitral regurgitation, but relieved 3-6 months after procedure. During one year of follow up, the majority of patients (16/20) were found in a good cardiac function, mitral area and the left atrial diameter, except in 4 patients with a high mitral score of more than 10. It is suggested that for patient with lower mitral morphological score and good general health, a larger diameter balloon might be suitable for effectively improving patient's symptom, but for patients with a previous surgical mitral commissurotomy, PBMV should not be selected.

Adult↗

Interpretation of cardiac pathophysiology from pressure waveform analysis: pacemaker hemodynamics.

The abnormal sequence of A-V contraction produces alteration of right and left heart hemodynamics reflecting the inappropriate timing of atrial contraction to ventricular filling. Some symptomatic patients may require A-V sequential pacing to improve cardiac output. The clinical effects of the atrial contribution to left ventricular function can be demonstrated by careful review of hemodynamic tracings in these individuals.

Aged↗

Negative inotropic actions of nitric oxide require high doses in rat cardiac muscle.

Initial experiments were designed to determine if vasoactive concentrations of nitric oxide (NO) alter contractility in rat heart. Contractile function was monitored in left atrial and papillary muscles (30 degrees C; paced at 0.5 Hz) during cumulative addition of 3-morpholino-sydnonimine-HCl(SIN-1), an agent that releases NO. At concentrations between 10(-7) and 10(-4) M (NO concentrations of approximately 10(-8)- 3 x 10(-7) M), SIN-1 did not affect contractility in either tissue. Similarly, 10(-4) M SIN-1 did not alter the positive inotropic responses to isoproterenol or increasing extracellular [Ca+2] ([Ca+2]o). To obtain higher concentrations of NO, additional studies were conducted using authentic NO. NO-saturated stock solutions and a corresponding control solvent were adjusted to pH 1.6 with HCl. Dose-dependent effects of NO were examined by adding aliquots of the stock solutions (or control solvent) to the bathing solution. At final concentrations of 1 x 10(-5)- 5 x 10(-4) M, NO produced transient, concentration-dependent decreases in contractility that were paralleled by reductions in buffer pH. Control solvent elicited similar reductions in pHo and transient decreases in contractility; however, the negative inotropic action elicited by the NO-containing solution was approximately 20% greater than that observed in control conditions. These data demonstrate that only high concentrations of NO depress contractility in isolated rat cardiac muscle, and suggest that this effect is mediated by both acidosis and a pHo-independent mechanism.

Animals↗