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PubMed2004

A novel framework of circulatory equilibrium.

A novel framework of circulatory equilibrium was developed by extending Guyton's original concept. In this framework, venous return (CO(V)) for a given stressed volume (V) was characterized by a flat surface as a function of right atrial pressure (P(RA)) and left atrial pressure (P(LA)) as follows: CO(V) = V/W - G(S)P(RA) - G(P)P(LA), where W, G(S), and G(P) denote linear parameters. In seven dogs under total heart bypass, CO(V), P(RA), P(LA), and V were varied to determine the three parameters in each animal with use of multivariate analysis. The coefficient of determination (r(2) = 0.92-0.99) indicated the flatness of the venous return surface. The averaged surface was CO(V) = V/0.129 - 19.61P(RA) - 3.49P(LA). To examine the invariability of the surface parameters among animals, we predicted the circulatory equilibrium in response to changes in stressed volume in another 12 dogs under normal and heart failure conditions. This was achieved by equating the standard surface with the individually measured cardiac output (CO) curve. In this way, we could predict CO [y = 0.90x + 5.6, r(2) = 0.95, standard error of the estimate (SEE) = 8.7 ml.min(-1).kg(-1)], P(RA) (y = 0.96x, r(2) = 0.98, SEE = 0.2 mmHg), and P(LA) (y = 0.89x + 0.5, r(2) = 0.98, SEE = 0.8 mmHg) reasonably well. We conclude that the venous return surface accurately represents the venous return properties of the systemic and pulmonary circulations. The characteristics of the venous return surface are invariable enough among animals, making it possible to predict circulatory equilibrium, even if those characteristics are unknown in individual animals.

Animals↗
PubMed1987

Binding and functional effects of atrial natriuretic factor in isolated rat kidney.

A new methodological approach was developed to study the relationship between specific binding and dose-response curves of the renal effects of atrial natriuretic factor (ANF) in isolated perfused rat kidneys (IK). IK were perfused with 125I-labeled and unlabeled ANF 1-28 (4 pM to 1 microM) to determine the following: 1) distribution, capacity (Cmax), and apparent affinity (S50) of specific binding of ANF 1-28 in cortex, outer medulla, and papilla and 2) dose-response curves of the effects of ANF 1-28 on renal hemodynamics and excretion of fluid and electrolytes. The kidney had a very high density of high-affinity binding sites for ANF. Cortex had greater than 90% of total binding sites (Cmax = 6.8 pmol/g tissue; S50 = 54 pM), whereas papilla had less than 2% of total binding sites with a 10-fold lower apparent affinity (S50 = 860 pM) than in cortex. ANF-induced increases in glomerular filtration rate and excretion of fluid and electrolytes were detectable at 10-100 pM and maximal effects occurred at 1-10 nM ANF. Below 1 nM there was no dissociation between the renal hemodynamic and natriuretic effects of ANF. There was a close agreement between dose-response and binding curves of ANF to cortex. Results demonstrate that binding site occupancy in kidney cortex and renal effects of ANF occur at near physiological concentrations of the hormone.

Animals↗
PubMed2001

[Structural and electrophysiological characteristics of the heart function during paroxysmal atrial fibrillation].

AIM: To examine structural and electrophysiological predictors of the onset and establishment as chronic of cardiac fibrillation (CF). MATERIAL AND METHODS: Echocardiography, transesophageal electrophysiological examination of the heart were performed in 420 cases of paroxysmal cardiac fibrillation (PCF). They were diagnosed as having new-onset (n = 68), rare (n = 92) and frequent (n = 260) PCF. RESULTS: Compared to healthy subjects, PCE patients had larger size of the left atrium (LA), higher atrium/ventricle value, lower frequency threshold of arrhythmia induction, decreased left atrial effective refractory period, longer induced paroxysm and maximal atrial response. CF chronicity can be predicted with the frequency threshold of arrhythmia induction under 300 imp/min, left atrial effective refractory period under 220 ms, left atrial size over 42 mm, induction of persistent PCF. CONCLUSION: A significant correlation was found between left atrial size and electrophysiological parameters of the heart characterizing arrhythmogenic "readiness" of the atria. This suggests a provoking role of left atrial dilatation in PCF.

Atrial Fibrillation↗
PubMed2004

Modern aspects of antithrombotic treatment: an introduction.

Intracardiac thrombosis and cardioembolisms may have impressive effects on quality of life, prognosis and therapeutic costs in patients with valve disease or replacement devices. Distinct pathophysiological differences exist regarding intracardiac thrombus formation in low-versus high-pressure areas. Important cardiac confounders for low-pressure areas are left atrial geometry and function, including atrial fibrillation or loss of active atrial contraction. In high-pressure areas, flow velocity and shear stress are raised, and this may result in flow turbulence, for example when blood passes a stenotic area. Other major factors which correlate with intracardiac thrombus formation are implantation of polymer material and the degree of endocardial damage resulting for example, from infective or rheumatic endocarditis. Because of the interaction of platelets and the plasma clotting system, a combination of oral anticoagulation therapy and antiplatelet drugs should prevent more thromboembolic events than might anticoagulation alone. Recent studies in patients with prosthetic heart valves have indicated a positive risk-benefit profile if low-dose antiplatelet drugs are added to moderate intensive oral anticoagulation therapy. Thromboembolic events and bleeding complications due to oral anticoagulation therapy are accepted key parameters to demonstrate the superiority of one replacement device over another. However, there is no consistent system for reporting morbid events. In order to organize low and narrow target INR ranges, point-of-care patient self-testing modalities have been introduced and used effectively in large sample sizes. In the near future, some promising new drugs--including direct thrombin or factor Xa inhibitors with broader therapeutic ranges and thus fewer side effects--will become available. The test for these drugs will be their potential to prevent intracardiac thrombosis and cardioembolism in a patient population which is under significant risk.

Anticoagulants↗
PubMed1988

Functional beta 2-adrenoceptors in right atria isolated from footshock-stressed rats.

The participation of beta 2-adrenoceptors in the chronotropic response was evaluated in right atria isolated from rats submitted to daily footshock stress for three days. Footshock increased both the sensitivity to salbutamol and the pA2 of butoxamine. These results provide additional support for the proposal that repeated footshock stress increases the function of rat atrial postjunctional beta 2-adrenoceptors.

Albuterol↗
PubMed1987

Functional heterogeneity of atrial natriuretic factor receptor in bovine adrenal zona glomerulosa is explained by an amiloride-sensitive high affinity molecular complex.

The effects of amiloride on the molecular characteristics of the atrial natriuretic factor (ANF) receptor from bovine adrenal zona glomerulosa were studied by computer modeling of competitive binding data, by affinity labeling experiments, and by steric exclusion high performance liquid chromatography of solubilized receptor. The order of potency of a series of truncated ANF analogs in competing for 125I-ANF binding to bovine adrenal zona glomerulosa membranes was the same as that obtained for inhibition of aldosterone secretion. Deletion of amino acids at the COOH-terminal end drastically reduced the affinities of the peptides. Computer analysis of competition curves revealed that all ANF analogs tested show similar binding characteristics: shallow competition curves, discrimination of varying proportions of high and low affinity binding states, and sensitivity to amiloride which increases the proportion of the high affinity binding component. These results from binding studies are suggestive of potential heterogeneity of ANF binding sites. In contrast, results from affinity cross-linking experiments are consistent with the notion of a single receptor protein. Incubation of membranes with increasing concentrations of 125I-ANF-(99-126) up to 3 nM resulted in the labeling of a single band of Mr 130,000. The ability of ANF analogs to compete for the labeling of the Mr 130,000 band by 125I-ANF-(99-126) agreed well with their potency as inhibitors of 125I-ANF binding to intact membranes. Addition of amiloride caused a dose-dependent increase in the labeling of the Mr 130,000 band. A single Mr 130,000 band was also labeled in bovine aorta and LLC-PK1 cell membranes. In order to further investigate the molecular basis for the apparent heterogeneity of ANF binding we have prelabeled the membrane receptor with 125I-ANF-(99-126) prior to solubilization with octyl-beta-D-glucoside and chromatography on a Superose 6 steric exclusion column. The elution profile of the prelabeled receptor consistently showed two peaks of radioactivity with mean Stokes radii of 70 and 50 A. When amiloride was added to the incubation medium, the elution profile consisted almost exclusively of the 70-A peak. Quantitative analysis of the chromatographic profiles revealed that amiloride increases by 2-3 times the area of the 70-A peak. We conclude that the 70-A form represents a ternary complex of the receptor with an amiloride-sensitive effector protein.

Adrenal Cortex↗
PubMed1981

[Diagnostic transesophageal atrial stimulation as a sinus node function test. I. Normal values and comparison with right atrial stimulation].

For the non-invasive functional analysis of the sinus node diagnostic transoesophageal atrial stimulations were performed. By means of transoesophageal premature individual stimulation we succeeded in a calculation of the so-called sinuatrial conduction time in 112 of 118 normal persons (ESACT = 103 +/- 23.5 ms). In comparison to the results in right-atrial stimulation the transoesophageally established times were 20 to 30 ms longer. By means of transoesophageal atrial stimulation with higher frequency in 64 healthy test persons the recreation time of the sinus node was determined in 64 healthy test persons (ESNRT = 968 +/- 218 ms). Taking into consideration the double standard deviation in an upper limit of 1,400 ms was the result which corresponds to the limit in intraatrial stimulation. In the direct comparison of the transoesophageal and right-atrial stimulation technique in patients with and without syndrome of the sinus node for the sinuatrial conduction time (r = 0.81, n = 51) as well as for the recreation time of the sinus node (r = 0.90, n = 36) relatively good correspondences were found. In the transoesophageal stimulation, however, the larger distance of the place of stimulation from the marginal area of the sinus node, the conduction of the impulse over the left to the right atrium as well as a possible vagal irritation are to be taken into consideration.

Adult↗
PubMed2003

Doppler transmitral flow indexes and risk of atrial fibrillation (the Framingham Heart Study).

Atrial fibrillation (AF) is characterized by structural remodeling and atrial systolic failure. It is unclear if atrial filling abnormalities precede the onset of AF. We evaluated 942 Framingham Study subjects (587 women; mean age 75 years) who underwent Doppler echocardiographic evaluation at a routine examination and who did not have a history of AF. We used multivariable Cox regression models (stratified by gender and prevalent cardiovascular disease) to examine the relations of Doppler transmitral flow indexes (ratio of the velocity-time integrals of the early [E] and late [A] diastolic filling waves [VTI E/A], a correlate of atrial conduit function; E-wave deceleration time; the atrial filling fraction, an index of atrial systolic function; and peak A wave velocity) to the incidence of AF. At follow-up (mean 7 years), 85 subjects (41 women) developed AF. In models adjusting for established risk factors for AF (including left atrial size) at baseline, and for heart failure and myocardial infarction on follow-up, a 1 SD increment in VTI E/A was associated with a 28% increase in risk of AF (hazards ratio 1.28, 95% confidence interval 1.02 to 1.59). A 1 SD decrease in the atrial filling fraction was associated with a 28% higher risk of AF (hazards ratio 1.28, 95% confidence interval 0.98 to 1.67). There was a U-shaped relation between peak A-wave velocity and risk of AF. Thus, in our elderly community-based sample, increased VTI E/A and a low atrial filling fraction were markers of increased risk of AF, suggesting that altered atrial filling may antedate AF.

Aged↗
PubMed1998

Radiofrequency and cryoablation of atrial fibrillation in patients undergoing valvular operations.

BACKGROUND: Previous studies have shown that the maze operation can restore sinus rhythm and atrial transport function in patients with chronic atrial fibrillation. The purpose of this study was to test the feasibility of the application of radiofrequency and cryoablation as an alternative to the classic maze operation. METHODS: Twelve patients undergoing mitral valve procedures were included in this study. Radiofrequency and cryoablation were applied to create lesions in both atria to simulate the classic maze operation. RESULTS: There were two surgical deaths. At the mean follow-up of 10.25 months for the remaining 10 patients; 6 were in sinus rhythm, 2 in atrial rhythm, 1 in paroxysmal atrial tachycardia, and 1 in atrial fibrillation. Doppler echocardiography at 6-month follow-up showed emergence of biatrial transport function in 3 patients and right atrial contractility in 8. At 12-month follow-up of 5 patients, Doppler echocardiography showed biatrial transport function in 3 and right atrial contractility in 4. CONCLUSIONS: Our modified maze procedure during valvular operation is effective for achieving an acceptable success rate to restore sinus rhythm and atrial transport function in patients with chronic atrial fibrillation.

Adult↗
PubMed2026

Histological Determinants of Atrial Dysfunction in Patients With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with diverse histological abnormalities, but their contributions to atrial dysfunction and functional recovery remain unclear. METHODS: In a discovery cohort of 375 patients with nonvalvular AF undergoing catheter ablation, atrial biopsy samples were quantitatively analyzed for fibrosis, intercellular space expansion, myofibrillar loss, myocardial nuclear density, and amyloid deposition. Left atrial reservoir strain (LASr) was assessed as a measure of atrial function during sinus rhythm (Group 1) or AF (Group 2) at the time of echocardiography. Functional recovery was defined as the change in LASr 12 months after ablation. Findings were validated in an independent cohort of 191 patients with AF. A subset of samples was additionally analyzed for DNA damage markers, poly(ADP-ribose), and phosphorylated histone H2A.X. RESULTS: LASr improved significantly after ablation in Group 2 but not in Group 1. Multivariable analyses identified greater fibrosis, reduced myocardial nuclear density, and advanced amyloid deposition as significant determinants of impaired atrial function in both groups and of limited postablation functional recovery in Group 2 (all P<0.01). Amyloid deposition was also significantly associated with adverse clinical outcomes. Decision-tree models incorporating LASr accurately identified advanced amyloid deposition in both cohorts (accuracy, 94%-96%). DNA damage markers were inversely associated with myocardial nuclear density and positively associated with cardiomyocyte hypertrophy. CONCLUSIONS: Fibrosis, DNA damage-associated reduction in myocardial nuclear density, and advanced atrial amyloidosis are key determinants of atrial dysfunction and impaired postablation functional recovery in patients with AF. LASr enables noninvasive identification of advanced atrial amyloidosis.

Humans↗