Markers of thrombin generation are associated with myocardial necrosis and left ventricular impairment in patients with ST-elevation myocardial infarction.

INTRODUCTION: Platelet activation, thrombin generation and fibrin formation play important roles in intracoronary thrombus formation, which may lead to acute myocardial infarction. We investigated whether the prothrombotic markers D-dimer, pro-thrombin fragment 1 + 2 (F1 + 2) and endogenous thrombin potential (ETP) are associated with myocardial necrosis assessed by Troponin T (TnT), and left ventricular impairment assessed by left ventricular ejection fraction (LVEF) and N-terminal pro b-type natriuretic peptide (NT-proBNP). MATERIALS/METHODS: Patients (n = 987) with ST-elevation mycardial infarction (STEMI) were included. Blood samples were drawn at a median time of 24 h after onset of symptoms. RESULTS: Statistically significant correlations were found between both peak TnT and D-dimer (p < 0.001) and F1 + 2 (p < 0.001), and between NT-proBNP and D-dimer (p = 0.001) and F1 + 2 (p < 0.001). When dividing TnT and NT-proBNP levels into quartiles there were significant trends for increased levels of both markers across quartiles (all p < 0.001) D-dimer remained significantly associated with NT-proBNP after adjustments for covariates (p = 0.001) whereas the association between NTproBNP and F1 + 2 was no longer statistically significant (p = 0.324). A significant inverse correlation was found between LVEF and D-dimer (p < 0.001) and F1 + 2 (p = 0.013). When dichotomizing LVEF levels at 40 %, we observed significantly higher levels of both D-dimer (p < 0.001) and F1 + 2 (p = 0.016) in the group with low EF (n = 147). SUMMARY/CONCLUSION: In our cohort of STEMI patients we demonstrated that levels of D-dimer and F1 + 2 were significantly associated with myocardial necrosis as assessed by peak TnT. High levels of these coagulation markers in patients with low LVEF and high NTproBNP may indicate a hypercoagulable state in patients with impaired myocardial function.

Tissue Doppler imaging describes diastolic function in men prone to develop hypertension over twenty years.

AIMS: Hypertension is one of several risk factors of cardiovascular disease and is associated with left ventricular (LV) systolic and diastolic dysfunction. A method for reliably detecting the onset of LV dysfunction before transition to irreversible damage of the myocardium would be of crucial importance in subjects with essential hypertension. METHODS AND RESULTS: Subjects with clear differences in BP level, development and duration of the hypertensive disease were examined at the age of 60 yrs: normotensives (n = 17), new hypertensives who developed hypertension over a 20 year period (n = 15) and hypertensives (n = 19). Relationships between conventional echocardiographic and tissue velocities imaging (TVI) parameters compared to LV parameters, and TVI as an estimate of LV function were explored. E'(Lat) (TVI peak early diastolic velocity) (P = 0.006) and E/E'(Lat) (P = 0.002) demonstrated differences in diastolic function between the groups. There were no significant differences regarding systolic myocardial velocities. E'(Lat) correlated to S'(Lat) (TDI peak systolic velocity) (r = 0.32, P = 0.026) and was independently predicted by S'(Lat) (R(2) = 0.24, P = 0.025) in multivariate analysis. E'(Lat) correlated negatively to LV mass index (r = -0.34, P = 0.012), also in multivariate regression analysis (R(2) = 0.12, P = 0.032). CONCLUSIONS: Myocardial diastolic velocities and mitral flow to annulus velocity ratio differentiated LV function between the hypertensive and normotensive groups. The parameters probably reflect changes in relaxation, recoil and contraction and parallel changes in LV mass index.

Effects of treatment with a 5-HT4 receptor antagonist in heart failure.

BACKGROUND AND PURPOSE: Positive inotropic responses (PIR) to 5-hydroxytryptamine (5-HT) are induced in the left ventricle (LV) in rats with congestive heart failure (CHF); this is associated with upregulation of the G(s)-coupled 5-HT(4) receptor. We investigated whether chronic 5-HT(4) receptor blockade improved cardiac function in CHF rats. EXPERIMENTAL APPROACH: Rats were given either the 5-HT(4) antagonist SB207266 (0.5 mg kg(-1) 24h(-1); MI(int)) or placebo (MI(pl)) through mini-osmotic pumps for 6 weeks subsequent to induction of post-infarction CHF. In vivo cardiac function and ex vivo responses to isoprenaline or 5-HT were evaluated using echocardiography and isolated LV papillary muscles, respectively. mRNA levels were investigated using real-time quantitative RT-PCR. KEY RESULTS: LV diastolic function improved, with 4.6% lower LV diastolic diameter and 24.2% lower mitral flow deceleration in MI(int) compared to MI(pl). SB207266 reduced LV systolic diameter by 6.1%, heart weight by 10.2% and lung weight by 13.1%. The changes in posterior wall thickening and shortening velocity, cardiac output, LV systolic pressure and (dP/dt)(max), parameters of LV systolic function, did not reach statistical significance. The PIR to isoprenaline (10 microM) increased by 36% and the response to 5-HT (10 microM) decreased by 57% in MI(int) compared to MI(pl). mRNA levels for ANP, 5-HT(4(b)) and 5-HT(2A) receptors, MHCbeta, and the MHCbeta/MHCalpha -ratio were not significantly changed in MI(int) compared to MI(pl). CONCLUSIONS AND IMPLICATIONS: Treatment with SB207266 to some extent improved in vivo cardiac function and ex vivo myocardial function, suggesting a possible beneficial effect of treatment with a 5-HT(4) receptor antagonist in CHF.

Apparent lack of beta 2 adrenergic receptors in porcine myocardium.

The aim of this study was to investigate the relative numbers of myocardial beta 1 and beta 2 receptors in pigs. Membrane particles from left ventricular porcine and mixed ventricular rat myocardium were examined for subtypes of beta adrenergic receptors with a radioligand binding technique using [125I]-cyanopindolol (ICYP) as trace, and the new highly beta 1 selective antagonist Sandoz 204 545 and the beta 2 selective antagonist ICI 118 551 for displacement. Radioligand displacement experiments were also performed using propranolol, isoprenaline and terbutaline. The displacement curves obtained with the subtype selective antagonists and agonist revealed biphasic inhibition of specific ICYP binding in rat preparations, indicating a beta 1/beta 2 ratio of approximately 2/1. In porcine preparations displacement of specific ICYP binding with all agents resulted in monophasic curves, thus sharply contrasting the rat preparations. Affinity constants of displacing drugs derived from these monophasic curves indicated that the specific binding site was a beta 1 receptor. No displacement compatible with beta 2 affinity was found. In the same rat preparations we found that adenylate cyclase activation and inhibition by beta receptor subtype specific agonists and antagonists were mediated by two receptor subtypes, whereas in the pig, adenylate cyclase activation and its inhibition seemed to occur via only one receptor subtype, the beta 1 adrenoceptor.

Effects of chronic amiodarone treatment on human myocardial beta adrenoceptor density and adenylate cyclase response.

STUDY OBJECTIVE: The aim of the study was to evaluate the effect of chronic treatment by amiodarone on beta adrenoceptor density and adenylate cyclase response in human myocardium. DESIGN: Density of beta 1 and beta 2 adrenoceptors was measured by radioligand binding assay. beta Adrenoceptor stimulated production of cAMP was measured by adenylate cyclase assay. EXPERIMENTAL MATERIAL: Right auricular tissue from five patients on chronic amiodarone treatment was compared with that from nine patients in similar clinical and haemodynamic state undergoing coronary bypass surgery. MEASUREMENTS AND MAIN RESULTS: beta 1 and beta 2 adrenoceptor subtypes were quantified using the highly beta 1 selective antagonist Sandoz 204 545. The total beta adrenoceptor density was 28% lower in the amiodarone treated group than in the controls (42.0 v 58.3 fmol.mg-1 protein, p less than 0.02), beta 1 adrenoceptors were 25% lower (33.1 v 44.3 fmol.mg-1 protein, p less than 0.02), and beta 2 adrenoceptors were 36% lower (8.9 v 14.0 fmol.mg-1 protein, p less than 0.02). The cAMP production following non-selective beta adrenoceptor stimulation (isoprenaline 5 mumol.litre-1) was reduced by 38% in the amiodarone treated group (14.2 to 8.7 pmol.min-1.mg-1 protein, p = 0.05). Terbutaline stimulated cAMP production was reduced by 49% (8.3 to 4.3 pmol.min-1.mg-1 protein, p = 0.03). Fluoride stimulated cAMP production was not significantly different (9.4 v 8.4 pmol.min-1.mg-1 protein, p = 0.15). CONCLUSIONS: Chronic treatment with amiodarone is associated with a non-selective downregulation of beta adrenoceptors. beta Adrenoceptor stimulated cAMP production was also reduced. The "beta blocking effect" of amiodarone is probably related to downregulation of beta adrenoceptors.

Specific non-beta-adrenergic binding sites for 125I-iodocyanopindolol in myocardial membrane preparations: a comparative study between human, rat, and porcine hearts.

STUDY OBJECTIVE: The aim was to investigate observed differences in beta adrenergic and apparent non-beta-adrenergic binding of (-)[125I]-iodocyanopindolol (125I-ICYP). DESIGN: Binding parameters for several beta adrenergic agonists and antagonists were examined in radioligand binding assay, using 125I-ICYP as radioligand, in membranes prepared from myocardial tissue. SUBJECTS: Human right auricular myocardium was obtained from patients undergoing open heart surgery. Ventricular myocardium was from Norwegian landrace pigs and Wistar rats. MEASUREMENTS AND MAIN RESULTS: Specific binding of 125I-ICYP was observed. This was only partially competed for with high affinity by isoprenaline, noradrenaline, adrenaline, and atenolol. Considerable interspecies variations in the magnitude of specific non-beta-adrenergic (NBA) binding of 125I-ICYP were shown. The equilibrium constant of dissociation (Kd) of the specific NBA binding sites for 125I-ICYP was 0.3-0.4 nmol.litre-1, and the binding capacities were 20, 106, and 192 fmol.mg-1 protein in rat, human, and porcine myocardium, respectively. The NBA sites were heat sensitive and destroyed by trypsin. Association to NBA sites occurred more rapidly than to beta adrenoceptors. Dissociation of bound 125I-ICYP from NBA sites and beta adrenoceptors at 30 degrees C revealed first order kinetics with t1/2 of 19 min from NBA, as compared to 120 min from beta adrenoceptors. In all three species the ligand specificity for NBA sites was very similar and various adrenergic agonists and antagonists competed with 125I-ICYP binding with the following potencies: timolol greater than propranolol greater than ICI 118 551 greater than pindolol greater than Sandoz 204 545 greater than terbutaline greater than noradrenaline and adrenaline much greater than isoprenaline and atenolol. Of agonists and antagonists for other receptor systems, only the serotoninergic 5-HT2 antagonist ritanserin could displace 125I-ICYP from the NBA sites with relatively high affinity. CONCLUSIONS: 125I-ICYP and several beta adrenoceptor antagonists interact specifically with receptor like proteins other than beta adrenoceptors, and remarkable interspecies difference in the levels of myocardial NBA sites was observed.

Hormone-responsive adenylyl cyclase in the human fallopian tube.

Hormone-responsive adenylyl cyclase (AC) activity in biopsies from normal human Fallopian tubes was studied. Enzyme activity with a Km of 0.15 mmol/L and a maximum velocity of 13.8 pmol/mg.min in the basal condition was demonstrated. The addition of prostaglandin E1 (PGE1), PGE2, PGF2a, vasoactive intestinal polypeptide, isoproterenol, and terbutaline increased enzyme activity, with no change in the Km. Maximum stimulation of AC activity was obtained with PGE1, resulting in a 2- to 8-fold increase in AC activity. The response of AC to PGE1 revealed a possible topographical variation, with lowest responses to PGE1 in the isthmus. No such segmental variation in AC activity and response was seen after stimulation with PGF2a, vasoactive intestinal polypeptide, or isoproterenol.

Natriuretic peptides in patients with aortic stenosis.

BACKGROUND: Whereas atrial natriuretic peptide (ANP) is secreted mainly from cardiac atria, brain natriuretic peptide (BNP) is produced to a larger extent in ventricles. Their relative importance as markers of cardiac function and myocardial hypertrophy is not yet clarified. This study evaluated circulating BNP and ANP and the N-terminal part of their propeptides (NT-proBNP and NT-proANP) as markers of left ventricular hypertrophy and atrial pressure increase in patients with aortic stenosis. METHODS: The plasma concentrations of BNP, NT-proBNP, ANP, and NT-proANP were measured by radioimmunoassay in 67 patients with aortic stenosis. Peptide plasma concentrations were related to measurements obtained by cardiac catheterization and echocardiography. RESULTS: Receiver operating characteristic curves indicated that BNP and NT-proBNP performed best in the detection of increased left ventricular mass and NT-proANP in the detection of increased left atrial pressure. NT-proBNP was significantly increased in mild left ventricular hypertrophy (left ventricular mass index, 78 to 139 g/m(2)), whereas NT-proANP was not increased until left ventricular mass index was 141 to 180 g/m(2). CONCLUSIONS: Plasma BNP and NT-proBNP may serve as early markers of left ventricular hypertrophy, whereas ANP and NT-proANP reflect left atrial pressure increase. The repeated and combined measurements of natriuretic peptides might provide diagnostic information relevant to the evaluation of the stage of aortic stenosis.

Exercise capacity of heart transplant recipients: the importance of chronotropic incompetence.

BACKGROUND: Maximal exercise capacity is limited in patients after heart transplantation. The extent to which chronotropic incompetence contributes to this intolerance has not been well defined. METHODS: This prospective cross-sectional study examined the heart rate response to exercise and its relation to exercise capacity in 159 heart transplant recipients during progressive, symptom-limited, upright exercise. All prior exercise studies of heart transplant recipients that reported peak oxygen uptake and peak heart rate were also evaluated. RESULTS: Peak oxygen uptake was closely correlated with peak heart rate (r = 0.39, p < 0.001) and maximum increase in heart rate (r = 0.49, p < 0.001) during exercise by our patients. Similar correlations were found in the published studies for peak oxygen uptake versus maximal heart rate (r = 0.54, p < 0.05) and peak oxygen uptake versus increase in heart rate (r = 0.63, p < 0.02). The current study showed that the increase in heart rate from rest to peak exercise was significantly higher and the decline in heart rate after exercise significantly faster for patients 2 or more years after transplantation than for patients less than 2 years after transplantation (46 +/- 2 versus 38 +/- 1.9 beats/min, p < 0.05); the decline in heart rate 4 minutes after exercise was 27 +/- 1.8 versus 16 +/- 1.8 beats/min, respectively ( p < 0.001). CONCLUSION: The reduction in peak oxygen consumption, particularly during the first 2 years, appears to be related in part to chronotropic incompetence. Late after transplantation the heart rate response to exercise is greater and the decline in heart rate after exercise faster, suggesting possible autonomic reinnervation in some patients. Chronotropic incompetence may be an inadequate explanation of oxygen uptake impairment seen late after transplantation, when other factors such as myocardial dysfunction and intrinsic skeletal muscle abnormalities are of increasing importance.

Influence of the exercise protocol on hemodynamic, gas exchange, and neurohumoral responses to exercise in heart transplant recipients.

BACKGROUND: A gradual accommodation to increasing exercise loads has been recommended for exercise testing in denervated posttransplantation heart recipients. However, how the exercise protocol influence the hemodynamic, gas exchange, and hormonal response to exercise in this not been studied. METHODS: Nine heart transplant recipients tests incremental maximal bicycle ergometry tests in random order. Exercise stages of 1 and 3 minute durations were compared with matched work rate increments ranging between 30 and 40 W. Expiratory gas was measured continuously and arterial blood was sampled at each of the matched work rates. RESULTS: Total exercise duration was 6.4 +/- and 15.3 +/- 0.7 minutes for the 1-minute and 3-minute protocols, respectively. Maximal workload was significantly higher during the 1-minute versus the 3-minute protocol (238 +/- 9 versus 200 +/- 11 W, p < 0.001), but maximal oxygen uptake was not significantly different (25.5 +/- 1.1 versus 26.5 +/- 1.2 ml. min-1.kg-1). Hemodynamic, metabolic, and some hormonal parameters showed marked differences between the two protocols, with significantly higher responses observed during the 3-minute protocol for heart rate, ventilation, lactate, atrial natriuretic factor, and growth hormone. Catecholamine (epinephrine and norepinephrine) and insulin responses did not differ between the two tests. If expressed as a relative exercise intensity (percentage of maximal oxygen uptake) no differences in hormonal responses were observed between the two protocols, except for growth hormone response which remained higher during the 3-minute protocol. CONCLUSIONS: Although maximal oxygen uptake was independent of the exercise protocol in these heart transplant recipients, the exercise protocol has a major influence on the hormonal and metabolic response. The delayed response observed for oxygen uptake and hormonal responses suggests a significant physiologic lag time during the more rapidly incremental protocol. These differences should be taken into account when exercise is used as a method to evaluate the heart transplant recipient.

Beta-adrenoceptor mediated responses and subtypes of beta-adrenoceptors in cultured rat Sertoli cells.

Membrane particles from Sertoli cell cultures were examined for subtypes of beta-adrenoceptors with a radioligand binding technique using [125I]iodocyanopindolol and a beta 1-selective antagonist (Sandoz 204 545) or a beta 2-selective antagonist (ICI 118 551). Biphasic competition curves and modified Eddie-Hofstee plots revealed a relative distribution of approx. 80% beta 1-adrenoceptors and 20% beta 2-adrenoceptors. Only 45% of the adrenoceptor mediated stimulation of adenylyl cyclase activity was associated with beta 1-adrenoceptors, whereas the remaining 55% was mediated via beta 2-adrenoceptors. The subtype selective antagonists inhibited isoproterenol stimulated aromatization of testosterone to estradiol-17 beta in a concentration-dependent manner. Complete inhibition of beta 1-adrenoceptors resulted in a 45% reduction of estradiol-17 beta formation, whereas similar inhibition of beta 2-adrenoceptors resulted in only a 35% reduction. It is concluded that cAMP-dependent effects of beta-adrenergic agonists in Sertoli cells are mediated by activation of both beta 1- and beta 2-adrenoceptors. The discrepancy between the relative number of beta 1- and beta 2-adrenoceptors and their relative contribution to cAMP production and aromatization indicates that beta 2-adrenoceptors in Sertoli cells are more tightly coupled to the adenylyl cyclase system than beta 1-adrenoceptors. Furthermore, complete inhibition of either beta 1- or beta 2-adrenoceptors by subtype selective antagonists, demonstrates a substantial fraction of spareness between agonist activation of the adenylyl cyclase complex and aromatization.

Echocardiographic criteria for detection of postinfarction congestive heart failure in rats.

We evaluated postinfarction myocardial function in rats and determined echocardiographic criteria for congestive heart failure (CHF) using high performance echocardiography. Extensive myocardial infarction (MI) was induced in rats by left coronary occlusion. Sham-operated animals served as controls. Five weeks later, high-frame rate ( approximately 200 Hz), fully digitized, shallow-focus (10-25 mm), two-dimensional, M-mode and Doppler echocardiography was performed. A J-tree cluster analysis was performed using parameters indicative of CHF. Reproducibility was examined. The cluster analysis joined the animals into one Sham and two MI clusters. One of the MI clusters had clinical characteristics of CHF and elevated left ventricular end diastolic pressure. Among the echocardiographic variables, only posterior wall shortening velocity separated the failing and nonfailing MI clusters. We conclude that, by high frame rate echocardiography, it is possible to obtain high- quality recordings in rats. It is feasible to distinguish MI rats with CHF due to myocardial dysfunction from those without failure and to perform longitudinal studies on myocardial function.

Diastolic flow pattern in the normal left ventricle.

OBJECTIVES: This study sought to clarify the diastolic flow pattern in the normal left ventricle. BACKGROUND: During left ventricular filling, basally directed (retrograde) velocities are seen in the outflow compartment. These velocities may represent blood returned from the apical region or a shortcut at a more basal level. METHODS: Left ventricular flow patterns were identified in 18 healthy individuals (age 47 +/- 12 years) with the use of high frame-rate two-dimensional color Doppler and color M-mode Doppler echocardiography techniques. Intraventricular velocities were measured with single pulsed Doppler at 3 levels in both inflow and outflow compartments (posterolateral and anteroseptal parts of the left ventricle). RESULTS: During early transmitral flow acceleration, all intraventricular velocities were directed towards the apex. However, after peak early and late inflow velocities and during diastasis, retrograde velocities were identified in the outflow compartment. These retrograde velocities occurred earlier, and were higher, at the level of the deflected anterior mitral leaflet tip compared with more apical levels (P <.001). A velocity pattern was established, consistent with early intraventricular vortex formation behind both mitral leaflets. The vortex adjacent to the anterior leaflet subsequently enlarged to include a major part of the left ventricle. CONCLUSION: Uniform diastolic flow patterns were identified in the normal left ventricles. The findings suggest that both early and late diastolic filling start with an initial motion of a fluid column, succeeded by vortex formation, which explains retrograde flow in the outflow compartment.

Reversal of intraventricular flow propagation during isovolumic relaxation: A marker of anterior wall dysfunction.

BACKGROUND: Myocardial infarction induces left ventricular (LV) wall motion abnormalities during isovolumic relaxation (IVR) and may potentially alter intraventricular flow during this period. This study evaluated whether 2-dimensional color Doppler measurements of intraventricular flow during IVR were able to identify LV dysfunction caused by coronary artery disease. METHODS: Patients with single-vessel coronary artery disease and posterior wall infarction (21 patients) or anterior wall infarction (27 patients) were included. Eighteen healthy persons served as a control group. LV function was examined by 2-dimensional echocardiography, 2-dimensional color Doppler, and pulsed Doppler techniques. RESULTS: All normal persons (23.6 +/- 10.9 cm/s) and patients with posterior infarction (19.6 +/- 9.3 cm/s) had flow propagation towards LV apex during IVR. Patients with anterior wall infarction had reversed flow direction (-12.2 +/- 8.7 cm/s, P <.001). The echocardiographic wall motion score index of the 4 apical segments correlated well with flow velocities (r = -0.78, P <.001). CONCLUSION: Reversed flow propagation during IVR may become a sensitive clinical marker of regional ischemia.

Effects of chronic pindolol treatment on human myocardial beta 1- and beta 2-adrenoceptor function.

To evaluate the effects of chronic pindolol treatment on human myocardial beta-adrenoceptor, membrane preparations from right atrial auricles from patients on chronic pindolol treatment and from patients not treated with beta-blocker were compared with respect to specific binding of [125I]-iodocyanopindolol [( 125I]-ICYP) and adenylate cyclase (AC) activity. Pindolol treatment was associated with a 25% increase in total beta-adrenoceptor density (72.3 vs. 58.3 fmol/mg protein). This increase was due a 40% increase of the beta 1-adrenoceptor subtype (62.2 vs. 44.3 fmol/mg protein), while beta 2-adrenoceptor density was decreased by about 25% (10.0 vs. 14.0 fmol/mg). Isoprenaline 5 mumol/l (9.7 vs. 14.2 pmol/min/mg) and terbutaline 50 mumol/l (4.9 vs. 8.3 pmol/min/mg protein) stimulated adenylate cyclase activity was reduced, whereas fluoride (10 mmol/l) stimulated cAMP production to the same extent in both groups (9.4 vs 9.4 pmol/min/mg protein). Thus, chronic treatment with pindolol was associated with upregulation of the beta 1-adrenoceptors and a down-regulation of the beta 2-adrenoceptors. The total level of beta-adrenoceptors was slightly increased. In spite of this, adenylate cyclase activity and response was reduced.

Gas exchange and neurohumoral response to exercise: influence of the exercise protocol.

Maximal oxygen uptake varies with the exercise protocol, but the extent to which hormonal and metabolic responses to exercise are influenced by the exercise protocol has not been precisely defined. Twelve healthy subjects underwent maximal exercise testing using two incremental bicycle tests with individualized, identical work rate increments between 40 and 70 W. One protocol employed a 1-min and the other a 3-min duration per stage. Expiratory gas and venous blood were sampled at regular intervals for metabolic and hormonal analysis. Exercise duration for the 1-min and 3-min protocols was 6.0 +/- 0.1 and 14.3 +/- 0.3 min, respectively (P < 0.001). Significantly higher values were observed for peak VO2 and maximal ventilation during the 3-min protocol compared with the 1-min protocol (41.1 +/- 1.8 vs 38.3 +/- 1.6 ml.kg-1.min-1, P < 0.001; and 104.9 +/- 8.0 vs 97.2 + 5.7 l.min-1, P < 0.05, for peak VO2 and peak ventilation, respectively). However, the maximal workload achieved was higher during the 1-min versus the 3-min protocol (330 + 24 vs 280 + 21 W, P < 0.01). No differences were observed for maximal heart rate or blood pressure, whereas maximal plasma lactate was roughly twice as high during the 3-min compared with the 1-min protocol (7.5 +/- 0.8 vs 3.8 +/- 0.5 mmol.l-1, P < 0.001). Norepinephrine, epinephrine, dopamine, and growth hormone levels were generally higher throughout exercise during the 3-min compared with the 1-min protocol. When expressed as a percentage of peak VO2, however, differences in catecholamine levels were not observed. Endothelin levels did not change. We conclude that the exercise protocol profoundly influences exercise capacity as well as the metabolic and hormonal response to exercise and should be considered when using these variables to evaluate an intervention.

Hemodynamic characterization of the CarboMedics mitral valve prosthesis.

BACKGROUND AND AIMS OF THE STUDY: The hemodynamic function of the CarboMedics bileaflet mitral valve prosthesis was evaluated by Doppler echocardiography and by heart catheterization. The clinical state of the invasively examined patients was evaluated before and after surgery. METHODS: Doppler echocardiography was performed in 54 patients at six months after surgery. Further, combined right and left heart catheterization was performed in 22 of these patients before surgery and at six months thereafter. RESULTS: The Doppler mean gradients were small (3.6 +/- 1.2 mmHg), and corresponded well with Doppler mean gradients in the subgroup examined with both methods (3.5 +/- 1.1 mmHg) and with the invasive gradients (3.4 +/- 1.9 mmHg); there was also no difference between the different valve sizes. Clinically, pressure recovery distal to the valve is probably so small that no systematic difference between the two techniques of measurement is present. Only physiological regurgitation was found, and no case of valve dysfunction. The patients improved from functional NYHA class 3.1 +/- 0.4 to 1.4 +/- 0.6, regardless of preoperative diagnosis, with most pronounced improvement in those with mitral stenosis. Pulmonary artery pressure was normalized. Pulmonary vascular resistance and cardiac index improved slightly. CONCLUSIONS: In conclusion, the valvular prostheses demonstrated excellent hemodynamic function. There was striking agreement between the small invasive and non-invasive gradients. Finally, the functional status of the patients improved considerably, most distinctly in those patients with prior mitral stenosis.

Left ventricular mass assessed by three-dimensional echocardiography using rotational acquisition.

BACKGROUND: The reproducibility of left ventricular (LV) mass measurement by two-dimensional (2-D) echocardiography is inadequate for individual assessments. HYPOTHESIS: This study was undertaken to evaluate the potential of LV mass determination with a new three-dimensional (3-D) echocardiographic method compared with 2-D measurements. METHODS: Porcine agarose-filled left ventricles (n = 15, true mass 61-511 g) of different shapes were measured by a multiplane 3-D method based on 90 images acquired by probe rotation axis (1) perpendicular and (2) parallel to the ventricular long axis ["parasternal" (the left sternal border was not present as a reference point in this study) and apical views]. Mass was also obtained using (3) the biplane truncated ellipsoid and (4) area-length methods, as well as (5) the modified cube formula. Five hearts were not analyzed with the apical 3-D technique because of insufficient image quality. RESULTS: Systematic deviation from true mass was small with all methods (< 5.3%). Accuracy, expressed as 1 standard deviation of individual estimates around this systematic bias, was 7.7, 13.6, 8.2, 11.9, and 11.9% of true mass for the methods 1-5, respectively. Interobserver reproducibility, expressed as the coefficient of variation, was 4.7, 8.8, 8.1, 8.9, and 9.4% for the same methods. CONCLUSION: Limits for individual accuracy and reproducibility of LV mass estimates are nearly doubled using apical compared with "parasternal" 3-D echocardiography in vitro. A main advantage of "parasternal" 3-D compared with 2-D LV mass estimates is better reproducibility, but at the expense of greater time consumption. Apical 3-D technique is not superior to simpler 2-D methods based on "parasternal" short axis imaging.

Effects of preload alterations on peak early diastolic mitral annulus velocities evaluated by tissue Doppler echocardiography.

BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography is proposed to be a relatively preload independent tool for assessment of diastolic function. No data exist on anaesthetized patients in whom myocardial contractility, vascular tone and baroreceptor reflexes are depressed. The aim of this study was to evaluate the effects of preload alterations on tissue velocities in patients during general anaesthesia for coronary arterial bypass surgery. METHODS: Fifteen patients referred for elective aorto-coronary bypass surgery were examined by tissue Doppler echocardiography. Early diastolic velocities in the septal and lateral portion of the mitral annulus were measured during preload interventions induced by tilting of the operating table in patients during general anaesthesia both before surgery and after chest closure. To verify changes in preload we used right atrial pressure and pulmonary artery occlusion pressure. RESULTS: Tissue velocities in both the septal and lateral portion of the mitral annulus were significantly higher when preload was increased, compared to when it was decreased. Alterations in diastolic velocities in the septal portion of the mitral annulus prior to surgery: 0.8 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.2 cm s-1, P < 0.001. Alterations in diastolic velocities in the lateral portion of the mitral annulus prior to surgery: 1.4 +/- 0.2 cm s-1, P < 0.001, after surgery: 1.1 +/- 0.3 cm s-1, P < 0.01. Concomitant changes in right atrial pressure and pulmonary artery occlusion pressure were 11 +/- 1 and 12 +/- 1 mmHg before surgery and 13 +/- 1 and 12 +/- 1 mmHg after surgery (P < 0.001 for all), respectively. CONCLUSION: These results show that tissue velocities of the mitral annulus are preload dependent in patients during general anaesthesia both before and after coronary surgery.

Defective excitation-contraction coupling in hearts of rats with congestive heart failure.

AIM: We examined the cellular basis for depressed cardiac contractility in rats with congestive heart failure (CHF) secondary to myocardial infarction. METHODS: Six weeks after ligation of the left coronary artery, CHF was confirmed by haemodynamic measures and echocardiographic demonstration of reduced myocardial contractility in vivo. Papillary muscles from CHF animals developed less force than those from sham operated (SHAM) animals. Cell shortening was measured in isolated ventricular myocytes voltage-clamped with high resistance electrodes. Ca2+ transients were measured in fluo-4 loaded myocytes. RESULTS: Contractions triggered by depolarizing test steps from a post conditioning potential of -70 mV were significantly smaller and had significantly reduced velocity of shortening in CHF compared with SHAM myocytes. However, contractions initiated from -40 mV, were similar in amplitude and velocity of shortening in CHF and SHAM cells. L-type Ca2+ current was not significantly different between CHF and SHAM cells, whether activated from -70 or -40 mV. Therefore, in SHAM cells, excitation-contraction coupling exhibited higher gain when contractions were initiated from negative (-70 mV), as compared with depolarized potentials (-40 mV). However, in CHF myocytes, excitation-contraction coupling gain was selectively depressed with steps from -70 mV. This depression of gain in CHF was not accompanied by a significant reduction in sarcoplasmic reticulum Ca2+ content. Isoproterenol increased Ca2+ transients less in CHF than SHAM myocytes. CONCLUSION: In this post-infarction model of CHF, the contractile deficit was voltage dependent and the gain of excitation-contraction coupling was selectively depressed for contractions initiated negative to -40 mV.