bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effects of pacing-induced and flow-limited ischemia on left ventricular function.
Authors: Applegate R J , Walsh R A , O'Rourke R A
Published: June 2011

We compared left ventricular (LV) myocardial blood flow and function accompanying severe demand ischemia (rapid atrial pacing in the presence of critical bilateral coronary stenoses) and supply ischemia (complete bilateral coronary occlusion) of the same ischemic regions in 14 pentobarbital-anesthetized dogs. Pacing-induced ischemia resulted in pronounced reductions in average regional epicardial blood flow (0.8 +/- 0.4 vs. control 1.2 +/- 0.4 [+/- SD] ml/g/min, p less than 0.05) and endocardial blood flow (0.4 +/- 0.1 vs. control 1.3 +/- 0.3 ml/g/min, p less than 0.05). More severe reductions in average regional epicardial and endocardial blood flow were seen after bilateral coronary occlusion (BCO) (0.3 +/- 0.3 and 0.1 +/- 0.1 vs. control 1.3 +/- 0.3 ml/g/min, p less than 0.05, respectively). Hemodynamics of postpacing ischemia (PPi) were consistently characterized by systolic impairment including depressed systolic contractile performance [(+)dP/dtmax 1,281 +/- 442 vs. control 2,173 +/- 775 mm Hg/sec, p less than 0.05], ventricular dilation (left ventricular [LV] end-diastolic dimension [EDD] 47.6 +/- 7.8 vs. control 44.7 +/- 8.6 mm, p less than 0.05), and an increase in LV end-diastolic pressure (EDP) (14.4 +/- 2.8 vs. control 4.2 +/- 2.8 mm Hg, p less than 0.05). Abnormalities in early and late diastolic function with PPi included increased time constant of isovolumic relaxation (78.0 +/- 40.4 vs. control 46.4 +/- 20.5 msec, p less than 0.05) and increased chamber stiffness (1.9 +/- 0.77 vs. control 0.81 +/- 0.55 mm Hg/mm, p less than 0.05), respectively. The LV diastolic pressure-dimension relation, however, shifted upward and to the right in eight of nine animals, whereas an upward shift was observed in only one animal. Thus, in this model of postpacing ischemia, we observed contractile failure and passive changes in diastolic function. Alterations in ventricular function occurred consistently earlier and to a greater extent during BCO than PPi, including higher LVEDP (25.3 +/- 8.1 vs. 14.9 +/- 6.6 mm Hg, p less than 0.05), greater ventricular dilation (delta LVEDD 4.9 +/- 2.5 vs. 3.5 +/- 2.8 mm, p less than 0.05), and reduced minor-axis dimension shortening (3.3 +/- 3.1% vs. 6.5 +/- 3.6%, p less than 0.05). To detect potential qualitative differences in ventricular function between the two types of ischemia, we evaluated hemodynamics at comparable loading conditions (30 seconds to 1 minute of BCO).(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of caffeine and ryanodine on delayed afterdepolarizations and sustained rhythmic activity in 1-day-old myocardial infarction in the dog.
Authors: Boutjdir M , el-Sherif N , Gough W B
Published: June 2011

Caffeine and ryanodine are known to modulate oscillatory release of Ca2+ from the sarcoplasmic reticulum. The effects of caffeine and ryanodine on delayed afterdepolarizations (DADs) and sustained rhythmic activity in subendocardial Purkinje fibers surviving 1-day-old myocardial infarction in the dog were studied with standard microelectrode techniques. In preparations that showed sustained rhythmic activity, a high concentration of caffeine (10 mM) and ryanodine (10(-7) and 10(-6) M) slowed and terminated the sustained rhythmic activity and markedly suppressed DADs. An increase in the temperature of the tissue bath from 37 degrees to 39 degrees C did not change these results. In quiescent normal and infarcted preparations, a low concentration of caffeine (0.5 mM) differentially induced DADs in ischemic but not in normal Purkinje fibers, increased the amplitude of existing DADs, and brought subthreshold DADs to threshold potential that caused triggered activity. Our results are consistent with the hypothesis that triggered activity arising from DADs characterizes the sustained rhythmic activity in endocardial preparations 1 day after infarction and indicate an important role for the sarcoplasmic reticulum in the genesis of DADs and triggered activity in this model.
Thallium 201 kinetics in stunned myocardium characterized by severe postischemic systolic dysfunction.
Authors: Moore C A , Cannon J , Watson D D , Kaul S , Beller G A
Published: June 2011

The hypothesis tested in this study was that despite the presence of severe postischemic myocardial dysfunction ("stunning"), the extraction and subsequent intracellular washout of thallium 201 should be preserved as long as irreversible sarcolemmal membrane injury was avoided. To produce myocardial stunning, 19 open-chested dogs with a critical left anterior descending coronary artery (LAD) stenosis underwent 10 5-minute periods of total LAD occlusion, each interspersed by 10 minutes of reperfusion by reflow through the critical stenosis. In another 12 control dogs observed for the same time period, no LAD occlusions were performed after placement of the critical stenosis. Hemodynamics, regional myocardial thickening by quantitative two-dimensional echocardiography, and microsphere-determined regional blood flows were serially measured. In 18 stunned dogs, systolic thickening in the LAD zone was markedly reduced to 0.4 +/- 2.4% at 40 minutes after the 10th reperfusion period compared with 32.5 +/- 2.2% thickening (p less than 0.001) in 12 control dogs at a matched time. The 201Tl first-pass extraction fraction determined by a double-isotope method using intracoronary 201Tl administration was comparable after the 10th reflow in a subgroup of 13 stunned (0.78) and six control (0.79) dogs. The T1/2 for the intracellular washout rate was also not significantly different in another group of six stunned (60 +/- 13 minutes) and six control (53 +/- 14 minutes) dogs, nor was the percentage of the 201Tl dose initially distributed in the interstitial compartment (11 +/- 3% vs. 7 +/- 2%). Systemic hemodynamics and regional flows were comparable in the two groups at 40 minutes after the 10th reflow. No dog had evidence of myocardial necrosis by triphenyl tetrazolium chloride staining. Thus, normal myocardial 201Tl extraction and washout kinetics are observed in a canine model of severe postischemic dysfunction (stunning) produced by repetitive brief LAD occlusions. These findings might have important clinical implications concerning the application of rest 201Tl scintigraphy for evaluation of perfusion and viability in patients with coronary artery disease and regional myocardial asynergy that is ultimately reversible.
Double-wave reentry as a mechanism of acceleration of ventricular tachycardia.
Authors: Brugada J , Boersma L , Kirchhof C , Brugada P , Havenith M , Wellens H J , Allessie M
Published: June 2011

By using a Langendorff-perfused ring of anisotropic rabbit epicardium, sustained reentrant ventricular tachycardia with a cycle length of 168 +/- 13 msec (n = 26) was induced by programmed electrical stimulation. Continuous left ventricular epicardial mapping with 256 simultaneously recorded unipolar electrograms demonstrated that the tachycardia was based on circuital movement of the impulse around a fixed obstacle. Because of the anisotropic properties of the myocardium, the circuit consisted of a ring with segments in which the circulating wave propagated slowly (20 +/- 2 cm/sec) or faster (62 +/- 4 cm/sec). This was related to transverse or longitudinal propagation in relation to fiber direction. In six of 26 experiments, sudden acceleration in rate of the tachycardia was observed during programmed electrical stimulation. This acceleration was caused by the occurrence of double-wave reentry (two successive waves traveling in the same direction and using the same circuit). In one of the experiments, induction of double-wave reentry was only possible at basal conditions but not after the administration of a class III antiarrhythmic drug. In a seventh experiment, induction of double-wave reentry became possible after the administration of a class IC antiarrhythmic drug. Because conduction velocity around the ring was depressed during acceleration, the total revolution time of the circuit during double-wave reentry was about 120% of that during single-wave reentry. Ventricular tachycardias in which double-wave reentry could be elicited had longer cycle lengths (197 +/- 11 vs. 156 +/- 8 msec, p less than 0.001) and larger excitable gaps (71 +/- 16 vs. 28 +/- 5 msec, p less than 0.001) than those not showing this phenomenon. Double-wave reentry might have important clinical implications in understanding ventricular tachycardia acceleration during programmed electrical stimulation, proarrhythmic effects of drugs, and pathophysiology of rapid ventricular tachycardias.
Effects of insulin on vasoconstriction induced by thromboxane A2 in porcine coronary artery.
Authors: Yanagisawa-Miwa A , Ito H , Sugimoto T
Published: June 2011

To elucidate the role of insulin in the control of coronary artery tone, its effects on porcine coronary artery contraction evoked by thromboxane A2 (TXA2) were studied in vitro. Ring preparations of porcine proximal coronary artery were suspended in a Magnus apparatus filled with Tyrode's solution at 37 degrees C and aerated with 100% O2, and the isometric tension of the contractions was measured. Insulin itself caused neither contraction nor relaxation. Insulin had no significant effect on the coronary artery contractions evoked by 20 mM K+, norepinephrine, histamine, and serotonin; however, 120 minutes of preincubation with a physiological concentration of insulin (30-300 muunits/ml) significantly accentuated coronary artery contractions evoked by STA2 (10(-11) to 10(-7) M), a stable analogue of TXA2 that is known to act on TXA2/prostaglandin H2 receptors (141.4 +/- 10.9% of the control at 10(-7) M STA2 in the presence of 300 muunits/ml insulin; p less than 0.01). The enhancing effects of insulin on the STA2-induced contractions were affected by extracellular glucose or magnesium ion concentrations. The enhancing effects of insulin were observed only at the glucose concentrations of 100-300 mg/dl and magnesium concentrations of 0.5-1.5 mM. Therefore, insulin was suspected of enhancing TXA2-induced contraction through a process that depends on extracellular glucose and Mg2+.
Persistent dysfunction of regenerated endothelium after balloon angioplasty of rabbit iliac artery.
Authors: Weidinger F F , McLenachan J M , Cybulsky M I , Gordon J B , Rennke H G , Hollenberg N K , Fallon J T , Ganz P , Cooke J P
Published: June 2011

This study investigated the vasodilator function of endothelium that regenerated after balloon angioplasty and the relation of this function to the extent of vascular injury and to subsequent intimal proliferation. Balloon angioplasty was performed in the left iliac artery of 47 New Zealand White rabbits. Vascular responses were examined in vitro 2 and 4 weeks after a "severe" injury (3.0-mm balloon) or a "moderate" injury (2.5-mm balloon). Both degrees of balloon injury caused complete endothelial denudation. Endothelial regrowth 2 weeks after either injury was confirmed histologically. Although the regenerated cells had irregular sizes and polygonal shapes and lacked the typical alignment in the direction of blood flow, immunocytochemical staining for factor VIII-related antigen identified these cells as endothelium. To study the vasodilator function of regenerated endothelium, rings of balloon-injured and control (contralateral) iliac arteries were suspended in organ chambers for recording of isometric force. Endothelium-dependent relaxation of balloon-injured vessels to acetylcholine and to the calcium ionophore A23187 were reduced at 2 and at 4 weeks after severe injury. After moderate injury, endothelium-dependent relaxations to these agents were reduced at 2 weeks but had normalized by 4 weeks. Endothelium-independent relaxation to sodium nitroprusside, however, was preserved in all study groups. Morphometric analysis revealed an inverse correlation between the degree of intimal thickening and maximal relaxation to acetylcholine (r = 0.45, p less than 0.01). Thus, there is a persistent attenuation of receptor- and nonreceptor-mediated endothelium-dependent relaxations after arterial injury. The regenerated cells have an altered morphological appearance, but staining for factor VIII-related antigen confirms their endothelial origin. The degree and duration of endothelial dysfunction depends on the severity of the initial injury and is related to the extent of intimal thickness.
Effect of right ventricular anatomy on the cardiopulmonary response to exercise. Implications for the Fontan procedure.
Authors: Rhodes J , Garofano R P , Bowman F O , Grant G P , Bierman F Z , Gersony W M
Published: June 2011

Incorporation of the right ventricle (RV) into the pulmonary circulation of patients with tricuspid atresia undergoing a Fontan procedure has been advocated. The consequences of this approach on the exercise function of these patients was studied by examining the effects of progressive and steady-state bicycle exercise tests performed by 11 patients with right atrial (RA)-RV Fontan anastomoses, seven patients with RA-pulmonary artery (PA) Fontan anastomoses, 13 patients after repair of tetralogy of Fallot, and 34 normal control patients. All patients were in New York Heart Association class I. The exercise function of the patients undergoing RA-RV and RA-PA Fontan procedures were similar. The achieved peak work loads 60% and 67% of control and peak oxygen consumptions 60% and 64% of control, respectively. Both groups also displayed excessive ventilation, elevated dead space/tidal volume ratios, and depressed cardiac output during steady-state exercise. In contrast, tetralogy of Fallot patients achieved peak work loads and oxygen consumptions 83% of control and maintained normal cardiac outputs and dead space/tidal volume ratios during steady-state exercise. These results suggest that the presence of an RV within the pulmonary circulation of the Fontan patient does not result in improved exercise function. This may be due to the development of obstructive gradients across the RA-RV conduits during exercise or to the RV's negative effect on left ventricular compliance. Moreover, in contrast with the postoperative tetralogy of Fallot patient, the hypoplastic RV of tricuspid atresia may not have sufficient myocardium to assume the active pumping function required by exercise.
Is standardization of left ventricular chamber elastance necessary?
Authors: Hsia H H , Starling M R
Published: June 2011

Because of the relation between left ventricular (LV) chamber elastance and heart size, it has been hypothesized that maximum time-varying elastance (Emax) must be standardized to differentiate between preserved and depressed LV systolic performance. To test this hypothesis, we studied 66 patients, of whom 25 had a normal LV, 20 had aortic regurgitation, 14 had mitral regurgitation, and seven had cardiomyopathy, with micromanometer-determined LV pressures and radionuclide angiograms during multiple LV loading conditions. Multiple regression analysis established that Emax was independently related to LV end-diastolic volume (r = -0.69). When the Emax and LV end-diastolic volume (EDV) data from all patients were plotted, a curvilinear relation was evident. Data transformation to the base e identified two distinct linear relations, one in the normal patients of lnEmax = -0.60 (lnEDV) +4.34 (r = -0.67, p less than 0.001); and one in the patients with cardiac pathology of lnEmax = -1.06 (lnEDV) +6.12 (r = -0.73, p less than 0.001), which differed from each other (p less than 0.01). When a mathematical standardization was applied to these data to eliminate the independent contribution of heart size to the reduction in lnEmax, the normal patients had a standardized lnEmax versus lnEDV slope of 0, whereas that in the patients with cardiac pathology remained negative and continued to differ from that in the normal patients (p less than 0.001). Dichotomization of patients with cardiac pathology into those with preserved and depressed LV chamber elastance by lnEmax or standardized lnEmax provided highly concordant data (k = 0.73, p less than 0.001). Moreover, the estimated contribution of LVEDV to the reduction in Emax in patients with cardiac pathology averaged only 14 +/- 7%. We conclude from these data that LV chamber elastance calculated with radionuclide angiography has an independent relation with LVEDV, that a mathematical standardization of Emax for heart size does not significantly alter the dichotomization of patients with cardiac pathology into those with preserved and depressed LV systolic performance, and that heart size makes a relatively small contribution to the reduction in this index of LV systolic performance. Thus, standardization for heart size may not be necessary to identify whether preserved or depressed LV chamber elastance exists in an individual adult patient with cardiac pathology compared with normal adult patients.
Three-dimensional left ventricular midwall dynamics in the transplanted human heart.
Authors: Ingels N B , Daughters G T , Stinson E B , Alderman E L , Miller D C
Published: June 2011

To quantify the three-dimensional regional dynamics of the left ventricular (LV) midwall and the centroid and cross-sectional shape of the LV chamber in the transplanted human heart, 12 miniature radiopaque tantalum markers were implanted in the LV midwall of the donor heart at the time of cardiac transplantation in 15 patients. Stereo cineradiography in the late postoperative period (mean, 52 days after surgery) allowed computer-aided measurements of the three-dimensional coordinates of multiple sites in anterior, inferior, lateral, and septal LV regions at 16.7-msec intervals throughout the cardiac cycle. In awake, supine patients, from maximum to minimum LV volume, group mean translations of free wall markers ranged from 0.80 to 1.24 cm, directed toward the LV interior, whereas translations of septal wall markers were significantly less, 0.46 and 0.34 cm (p less than 0.01), directed away from the LV interior. A component of this translation along the septal-lateral axis was also significantly less (p less than 0.01) in the septum (0.19 and 0.20 cm) than in the free wall, where it ranged from 0.32 to 0.97 cm. The LV cross section was not circular, and anterior-inferior dimensions (7.18 +/- 0.66 and 6.13 +/- 0.79 cm, at maximum and minimum volumes, respectively) were significantly greater (p less than 0.01) than septal-lateral dimensions (5.78 +/- 0.65 and 5.12 +/- 0.48 cm), yielding an unchanging transverse elliptical LV eccentricity (0.58 +/- 0.13). The position of the LV center of volume did not change significantly from maximum to minimum volume in the direction of either the LV long axis or the anterior-inferior axis, but it did change significantly (0.55 +/- 0.23 cm, p less than 0.01) along the septal-lateral axis. We conclude 1) as viewed in a fixed external reference system, midwall sites in the interventricular septum of the transplanted human heart move paradoxically yet are relatively immobile compared with the three-dimensional dynamics of midwall sites in the LV free wall; 2) the transverse cross-sectional shape of the LV in the transplanted human heart is decidedly oval, with significantly greater anterior-posterior than septal-lateral dimensions at the time of maximum and minimum LV volumes; and 3) the center of volume in the transplanted human LV is remarkably stable in the directions of the LV long axis and anterior-posterior axis, suggesting a balance of forces along these axes, yet it moves significantly toward the interventricular septum, presumably counterbalancing the opposite translation during systole of the right ventricular (RV) center of volume.(ABSTRACT TRUNCATED AT 400 WORDS)
Sympathoinhibitory effects of atrial natriuretic factor in normal humans.
Authors: Floras J S
Published: June 2011

In rats, atrial natriuretic factor (ANF) reduces sympathetic nerve activity (SNA) reflexively by sensitizing cardiac mechanoreceptors with inhibitory vagal afferents. We performed three series of experiments in 26 normal young men to document whether ANF inhibits SNA in humans and if so, to determine potential mechanisms for this phenomenon. First, we recorded muscle SNA before and during brief infusions of ANF, vehicle (saline solution), and sodium nitroprusside, titrated to achieve reductions similar to those produced by ANF in diastolic pressure and central venous pressure, and we also assessed the effect of ANF on sympathetic nerve responses to a cold pressor test (CPT). Second, we determined the effect of ANF on Doppler-derived measurements of cardiac output and responses to hypotensive (-40 mm Hg) lower-body negative pressure (LBNP) and its sudden cessation. Third, we applied nonhypotensive (-15 mm Hg) LBNP to selectively unload cardiopulmonary baroreceptors, and we released LBNP to stimulate these inhibitory afferents during sequential infusions of nitroglycerin, vehicle (saline solution), and ANF. Our key findings were that 1) reductions in arterial and central venous pressures during ANF infusion were not accompanied by anticipated reflex increases in muscle SNA; 2) ANF blunted the increase in SNA with CPT; 3) ANF increased stroke volume and cardiac output; and 4) sympathoneural responses to both the application and the sudden cessation of nonhypotensive LBNP were attenuated, not augmented, by ANF. Changes in plasma norepinephrine concentrations reflected these sympathetic nerve responses to ANF. These results do not support the concept that ANF inhibits sympathetic outflow reflexively in humans by increasing discharge from cardiac mechanoreceptors with inhibitory vagal afferents but are consistent with either a central or a ganglionic sympathoinhibitory action of ANF. ANF could facilitate hypotension and natriuresis in humans by attenuating the reflex sympathetic response to baroreceptor deactivation.
Preoperative risk evaluation and stratification of long-term survival after valve replacement for aortic stenosis. Reasons for earlier operative intervention.
Authors: Lund O
Published: June 2011

Predictability of prognosis was analyzed in 630 patients who were alive 30 days after valve replacement (1965-1986) for aortic stenosis. Follow-up totaled 4,072 patient-years. During the operative periods of 1965-1971 (n = 62), 1972-1976 (n = 164), 1977-1981 (n = 158), and 1982-1986 (n = 246), decreases in cardiothoracic index (0.56 +/- 0.06, 0.53 +/- 0.06, 0.52 +/- 0.06, and 0.51 +/- 0.06; p less than 0.0001), in the prevalence of functional classes III and IV (87%, 76%, 68%, and 62%; p less than 0.0001), and of left ventricular (50%, 39%, 36%, and 30%; p less than 0.05) were accompanied by improved survival (5 year/10 year +/- SE: 73 +/- 6%/53 +/- 6%, 82 +/- 3%/65 +/- 4%, 89 +/- 3%/79 +/- 4%, and 87 +/- 3%/-; p = 0.002) despite increasing age (56 +/- 9, 57 +/- 11, 59 +/- 10, and 61 +/- 11 years; p less than 0.01). A Cox regression analysis identified peak-to-peak systolic gradient (p = 0.0001; inversely related to death rate), cardiothoracic index (p = 0.0003), left ventricular failure (p = 0.0005), prosthetic orifice diameter of 15 mm or less (p = 0.001), age (p = 0.003), ventricular ectopic beats (p = 0.004), male gender (p = 0.03), and antianginal/antiarrhythmic treatment (p = 0.03) as independent risk factors. A prognostic index calculated from the final Cox model stratified the patients into eight risk groups, having observed +/- SE/predicted/expected (matched background population) 10-year survival rates of 90 +/- 7% (n = 29)/94%/91%, 84 +/- 6% (n = 61)/89%/87%, 86 +/- 3% (n = 105)/83%/81%, 75 +/- 4% (n = 165)/75%/77%, 62 +/- 6% (n = 128)/63%/74%, 51 +/- 8% (n = 84)/47%/71%, 29 +/- 9% (n = 40)/31%/67%, and 16 +/- 9% (n = 18)/14%/54% (p less than 0.000001/-/-). Excess mortality relative to the background populations prevailed predominantly in risk groups 5-8 and was mainly caused by congestive heart failure. Thus, improved long-term survival during the 22-year operative period was related to improved preoperative patient status. Earlier operation (= low prognostic index) inferred a survival rate comparable to that of a matched background population. The prognostic index was probably predominantly related to preoperative myocardial damage that caused late predictable death from congestive heart failure.
Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell'Angina Instabile Group.
Authors: Balsano F , Rizzon P , Violi F , Scrutinio D , Cimminiello C , Aguglia F , Pasotti C , Rudelli G
Published: June 2011

We conducted a controlled multicenter trial with central randomization and evaluation of events under blind conditions involving 652 patients with unstable angina. Patients were treated either with conventional therapy alone (group C) (n = 338) or with conventional therapy combined with an inhibitor of platelet aggregation, ticlopidine 250 mg b.i.d. (group C + T) (n = 314). Patients were assigned randomly within 48 hours of admission and followed up for 6 months. With the "intention-to-treat" approach, the primary end points, vascular death and nonfatal myocardial infarction, were observed in 13.6% of the patients in group C and in 7.3% of the patients in group C + T, which is a reduction in risk of 46.3% (p = 0.009). Vascular mortality was 4.7% in patients in group C and 2.5% in patients in group C + T, which is a reduction in risk of 46.8% (p = 0.139). The risk of nonfatal myocardial infarction was reduced by 46.1% (p = 0.039), with a frequency of 8.9% in patients in group C and 4.8% in patients in group C + T. New Q wave myocardial infarction occurred with a frequency of 6.8% in patients in group C and 3.8% in patients in group C + T, which is a reduction in risk of 44.1% (p = 0.091). Fatal and nonfatal myocardial infarction was 10.9% in patients in group C and 5.1% in patients in group C + T, which is a reduction in risk of 53.2% (p = 0.006). These findings confirm the importance of platelets in the pathogenesis of unstable angina and the usefulness of antiplatelet treatment for the prevention of cardiovascular events.
Cardiorenal actions of neutral endopeptidase inhibition in experimental congestive heart failure.
Authors: Cavero P G , Margulies K B , Winaver J , Seymour A A , Delaney N G , Burnett J C
Published: June 2011

The present studies were designed to determine the action of neutral endopeptidase inhibition (NEP-I), an inhibitor of the degradation of atrial natriuretic factor (ANF), in congestive heart failure (CHF). Studies were conducted in two groups of anesthetized dogs with CHF induced by 8 days of rapid right ventricular pacing. Group 1 (n = 5) received a specific NEP-I (SQ 28,603) at two doses administered sequentially -30 mg/kg followed by a 60 mg/kg i.v. bolus. Group 2 (n = 5) received intravenous infusion of exogenous ANF (100 ng/kg/min) to achieve increases in plasma ANF concentration as observed in group 1. NEP-I resulted in a diuresis and natriuresis (p less than 0.05) with increases in the fractional excretion of sodium and fractional excretion of lithium, the latter a marker for proximal tubule sodium delivery. Such tubular actions occurred in the absence of increases in glomerular filtration rate or renal blood flow but were associated with significant increases in urinary ANF and urinary cyclic GMP. Plasma ANF increased after the 30 mg/kg NEP-I dose. In contrast, in group 2 with exogenous ANF and despite a marked increase in plasma ANF, no natriuresis was observed. Arterial pressure did not change in either group. These studies demonstrate for the first time in CHF that NEP-I may potentiate the natriuretic action of endogenous ANF by a mechanism that is independent of systemic or renal hemodynamics and does not parallel increases in plasma ANF. These studies support an important therapeutic role for NEP-I in CHF.
Determination of right ventricular mass in humans and dogs with ultrafast cardiac computed tomography.
Authors: Hajduczok Z D , Weiss R M , Stanford W , Marcus M L
Published: June 2011

There is currently no clinical approach to precisely measure right ventricular (RV) mass. We postulated that the radiological mode of ultrafast computed tomography (CT) of 3-mm-thick slices with 0.7-mm resolution would allow sufficient resolution to accurately estimate RV mass. Using this radiological mode, we serially imaged the entire right ventricle from apex to base, gated to end diastole, and applied Simpson's rule to calculate mass of the RV free wall. Thirteen mongrel dogs (weight, 6-30 kg) were studied. The free wall mass of the right ventricle was in the range of 12.0-47.5 g and averaged 35.4 +/- 3.7 g (mean +/- SEE). The correlation between RV mass estimated by ultrafast CT and actual RV mass was r equaling 0.85, SEE equaling 5.5 g, slope equaling 0.99, and gamma intercept equaling -1.8. Intraobserver and interobserver variability (r = 0.99 and r = 0.99, respectively) was excellent with a standard deviation (SD) equal to 1.5 and 1.8, respectively. The effect of variable RV preload (right atrial pressure, -5 to +20 mm Hg) on accuracy of RV mass measurements produced minimal error (SD = 3.6 g) in RV mass measurements. Seven normal young healthy men were also studied. The free wall mass of the right ventricle was in the range of 48.3-67.4 g and averaged 54.6 +/- 2.8 g (mean +/- SEE). The left ventricular to right ventricular (LV:RV) ratio averaged 3.2 +/- 0.2:1. These results are in agreement with human autopsy data in healthy males reporting mean RV mass equal to 46 g and an LV:RV ratio equal to 3.4:1. Because imaging every 3-mm slice from apex to base requires two contrast injections, we determined the accuracy of RV mass measurements if only every fourth 3-mm slice with interpolation was used. RV mass measurements using every slice or every fourth slice with interpolation were excellent (dogs, r = 0.99; humans, r = 0.97). It is concluded that high resolution CT imaging (3-mm tomograms) allows accurate measurements of RV mass. It is possible to add this stop-action mode of ultrafast CT, to previous CT studies, using every fourth tomographic slice for mass determinations and only one additional contrast injection of 40-60 ml. This should permit the study of progression and regression of RV mass in patients with various diseases.
Effect of atrioventricular interval during pacing or reciprocating tachycardia on atrial size, pressure, and refractory period. Contraction-excitation feedback in human atrium.
Authors: Klein L S , Miles W M , Zipes D P
Published: June 2011

To determine whether a contraction-excitation feedback mechanism exists in human atrium, we investigated the effects of varying the atrioventricular (AV) interval from 0 to 360 msec during AV pacing at a cycle length of 400 msec on atrial pressure, size, and refractoriness in 10 patients (group 1, without supraventricular tachycardia). The same parameters were determined in another 10 patients (group 2, with different spontaneous AV relations) during AV reciprocating tachycardia or AV nodal reciprocating tachycardia and during high right atrial (RA) pacing at the tachycardia cycle length. In group 1 patients, peak and mean RA pressure, RA effective refractory period (RA-ERP), and left atrial (LA) size all decreased to minimal values at an AV interval of 120 msec and remained low as the AV interval was increased and approached 400 msec. The increase in each of the variables from its lowest to greatest value was as follows: Mean systemic blood pressure, 20.9 +/- 3.1 mm Hg; LA size, 0.55 +/- 0.05 cm; RA peak pressure, 10.4 +/- 1.8 mm Hg; RA mean pressure, 3.5 +/- 0.6 mm Hg; and RA-ERP, 22.5 +/- 3.0 msec, p less than 0.001 for each. The weighted mean correlation coefficient with RA-ERP was significant for RA peak pressure and LA size (p less than 0.001 for each). These same relations were investigated in five patients with the Wolff-Parkinson-White syndrome and AV reciprocating tachycardia and five patients with AV nodal reciprocating tachycardia (group 2).(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment and follow-up of pediatric survivors of sudden cardiac death.
Authors: Silka M J , Kron J , Walance C G , Cutler J E , McAnulty J H
Published: June 2011

In the young patient resuscitated from sudden cardiac arrest, the risks of recurrence are uncertain and so are the criteria defining therapeutic efficacy for the presumed cause of the initial event. In this study, we analyzed the outcome of 15 consecutive young patients, who were resuscitated from pulseless ventricular tachycardia or ventricular fibrillation and who were evaluated by comprehensive hemodynamic and electrophysiological testing. Patients were 11.2 +/- 2.7 (mean +/- SD) years old at the time of their event, and each was known to have some form of heart disease before sudden cardiac arrest. Ventricular tachycardia or fibrillation was inducible by programmed electrical stimulation in eight patients. Accessory atrioventricular connections, with antegrade effective refractory periods less than 220 msec, were identified in three patients. Sustained atrial flutter was the only arrhythmia inducible in two patients, and no arrhythmias were inducible in two other patients. Surgical or electrophysiological-guided medical therapy resulted in noninducibility of the ventricular arrhythmias in six patients. Surgical division of the accessory atrioventricular connections was performed in three patients, and arrhythmias were not inducible after operation. The four patients with atrial flutter or without defined arrhythmia were treated with an empiric therapy. During 37 +/- 14 months of follow-up, the nine patients with documented noninducibility of a defined cause of sudden cardiac arrest were free of recurrent events. In contrast, during 18 +/- 10 months of follow-up, two of the six patients with empiric therapy or persistent inducibility of ventricular tachycardia died suddenly, and three others had recurrence of ventricular tachycardia or fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrophysiological testing and nonsustained ventricular tachycardia. Use and limitations in patients with coronary artery disease and impaired ventricular function.
Authors: Wilber D J , Olshansky B , Moran J F , Scanlon P J
Published: June 2011

Electrophysiological testing was performed in 100 consecutive patients with spontaneous asymptomatic nonsustained ventricular tachycardia, chronic coronary artery disease, and ejection fraction of less than 40%. Fifty-seven patients without inducible sustained ventricular arrhythmias were discharged on no antiarrhythmic therapy. Sustained monomorphic ventricular tachycardia was induced in 37 patients, and polymorphic ventricular tachycardia or ventricular fibrillation was induced in six patients. Of the 43 patients with inducible sustained ventricular arrhythmias, three had spontaneous cardiac arrest during serial drug testing and were excluded from further analysis. Twenty patients were discharged on drug therapy, resulting in suppression of inducible sustained ventricular arrhythmias. The remaining 20 patients with persistently inducible sustained arrhythmias were discharged on drug therapy, resulting in maximal rate slowing of the induced tachycardia. During a mean follow-up of 16.7 months, there were 10 recurrent cardiac arrests or sudden deaths. The 1- and 2-year actuarial incidence of these events was 2% and 6%, respectively, in patients without inducible sustained ventricular arrhythmias; 0% and 11%, respectively, in patients in whom inducible arrhythmias were suppressed; and 34% and 50%, respectively, in patients with persistently inducible sustained ventricular arrhythmias. Multivariate Cox analysis identified only the persistence of inducible sustained ventricular arrhythmias as a significant independent predictor of sudden death or recurrent sustained arrhythmias (p less than 0.001; relative risk, 3.5; 95% confidence intervals, 2.1-4.9). In this population, therapeutic intervention to prevent sudden death is unnecessary in patients without inducible sustained ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
Prediction of successful outcome in 130 patients undergoing percutaneous balloon mitral valvotomy.
Authors: Abascal V M , Wilkins G T , O'Shea J P , Choong C Y , Palacios I F , Thomas J D , Rosas E , Newell J B , Block P C , Weyman A E
Published: June 2011

We studied 130 patients undergoing percutaneous balloon mitral valvotomy. The relation between valvular morphology according to a previously described echocardiographic scoring system and hemodynamic outcome expressed as qualitative ("good" and suboptimal) and as absolute change in valve area was analyzed. The relative importance of the individual components of this echocardiographic score (valvular thickening, mobility, calcification, and subvalvular disease) to the change in valve area after valvotomy was also examined. Mean transmitral pressure gradient decreased from 16 +/- 6 to 6 +/- 3 mm Hg (p less than 0.0001), and mitral valve area increased from 0.9 +/- 0.3 to 1.8 +/- 0.7 cm2 (p less than 0.0001). Results in individual patients were variable. Eighty-four percent (61 of 73) of patients with an echocardiographic score of 8 or less had a "good" outcome (final valve area greater than or equal to 1.5 cm2 and an increase in valve area of greater than or equal to 25%), whereas 58% (33 of 57) of patients with an echocardiographic score of 8 or more had a suboptimal result (p less than 0.001). The sensitivity of an echocardiographic score of 8 or less for predicting a "good" outcome was 72%, and the specificity was 73%. The echocardiographic score correlated negatively (r = -0.40, p less than 0.0001) with the absolute increase in mitral valve area after valvotomy, but there was substantial scatter in the data. Of the four components of the total echocardiographic score, valvular thickening correlated best with the absolute change in value area (r = -0.47, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Doppler-derived rate of left ventricular pressure rise. Its correlation with the postoperative left ventricular function in mitral regurgitation.
Authors: Pai R G , Bansal R C , Shah P M
Published: June 2011

A new Doppler-derived index of the rate of left ventricular (LV) pressure rise (delta P/delta t) was evaluated for the prognostic stratification of patients with chronic mitral regurgitation. The index is derived from the continuous wave Doppler mitral regurgitation signal by dividing magnitude of LV-left atrial pressure gradient rise (delta p) between 1 and 3 m/sec of the mitral regurgitation velocity signal by the time taken (delta t) for this change. We studied the LV delta P/delta t and other echocardiographic indexes of LV function before and after mitral valve surgery in 25 patients with chronic, severe mitral regurgitation in the absence of significant coronary artery disease. There was a good correlation between postoperative ejection fraction (EF) and the derived LV delta P/delta t (r = 0.75, p less than 0.001). The other echocardiographic parameters that correlated with postoperative EF were LV end-systolic dimension (r = -0.7, p less than 0.001), end-systolic volume (r = -0.69, p less than 0.001), end-diastolic dimension (r = -0.58, p less than 0.01), end-diastolic volume (r = -0.57, p less than 0.01), preoperative EF (r = 0.69, p less than 0.001), end-systolic wall stress (r = -0.61, p less than 0.01), and end-systolic wall stress normalized for end-systolic volume index (r = -0.45, p less than 0.05). With multiple regression, the LV delta P/delta t and LV end-systolic dimension (ESD) were shown to be independent predictors of postoperative EF. The postoperative EF could defined by the equation: 43 + 0.8 square root delta P/delta t--0.53 ESD (mm) (r = 0.86).(ABSTRACT TRUNCATED AT 250 WORDS)
Intermittent perfusion of ischemic myocardium. Possible mechanisms of protective effects on mechanical function in isolated rat heart.
Authors: Tani M , Neely J R
Published: June 2011

Intermittent restoration of coronary flow during ischemia reduced myocardial damage and improved recovery of function. The mechanisms of the protective effects of intermittent perfusion were investigated in isolated rat hearts. Ventricular function was assessed as the product of developed pressure (left ventricular systolic pressure minus end-diastolic pressure) and heart rate. Recovery of function was calculated by division of the product at the end of reperfusion by that before ischemia. After 40 minutes of sustained global ischemia, intracellular Na+ (Nai) increased from 11 to 74 mumol/g dry wt. During 30 minutes of reperfusion, these hearts took up a large amount of 45Ca2+ (10 mumol/g dry wt), recovered only 24% of preischemic function, and had an increased left ventricular end-diastolic pressure (48 mm Hg). When the 40-minute period of ischemia was interrupted at 10-minute intervals by intermittent perfusion (three periods of 3 minutes) with either oxygenated or hypoxemic buffer, Nai increased to only 12 or 17 mumol/g dry wt, and reperfusion resulted in much lower 45Ca2+ uptake (0.5 and 0.5 mumol/g dry wt, respectively). Recovery of function was 100% of the preischemic value. When hypoxemic buffer without glucose was used for intermittent perfusion, Nai increased to 50 mumol/g dry wt, ATP was depleted, and reperfusion resulted in reduced recovery of function (76%) and moderately increased 45Ca2+ uptake (2.1 mumol/g dry wt). The role of Na(+)-K+ pump activity in maintaining low Nai was assessed by removing K+ from oxygenated or hypoxemic buffers used during intermittent perfusion. Under these conditions, Nai rose to 64 or 102 mumol/g dry wt, 45Ca2+ uptake increased to 4.4 or 9.4 mumol/g dry wt, and recovery of function was poor. There was a highly significant correlation between Nai during ischemia and reperfusion Ca2+ overload (r = 0.87) or impaired recovery of function (r = 0.96). These results indicate that prevention of an increase in Nai by maintenance of Na(+)-K+ pump activity is associated with a reduction of Ca2+ overload through Na+/Ca2+ exchange.
Pericardial prostaglandin biosynthesis prevents the increased incidence of reperfusion-induced ventricular fibrillation produced by efferent sympathetic stimulation in dogs.
Authors: Miyazaki T , Zipes D P
Published: June 2011

This study tested the hypothesis that sympathetic neural stimulation increases the prevalence of reperfusion-induced ventricular fibrillation and explored the mechanisms by which this occurs and how it may be prevented. In anesthetized, autonomically denervated dogs, we examined the effects of bilateral ansae subclaviae stimulation (SS) and of induction of pericardial biosynthesis of prostaglandins, an intervention that reduces SS effects by acting at presynaptic sites. A 5-minute occlusion of the left anterior descending coronary artery distal to the first or second diagonal branch was performed during SS. Heart rate was maintained constant by atrial pacing. In the absence of SS, one of 23 dogs developed ventricular fibrillation during occlusion, and three of the remaining 22 dogs developed ventricular fibrillation upon reperfusion. SS did not increase the prevalence of occlusion-induced ventricular fibrillation (four of 23 dogs) but increased the prevalence of reperfusion-induced ventricular fibrillation (12 of the remaining 19 dogs, p = 0.01). SS did not affect occlusion-induced decrease in local electrogram amplitude recorded from the ischemic myocardium or myocardial blood flow to the ischemic myocardium during occlusion or reperfusion. SS, however, prevented occlusion-induced increase in diastolic excitability threshold. Instillation into the pericardial cavity of arachidonic acid solution (3 micrograms/ml) resulted in release of prostacyclin, measured by radioimmunoassay as a stable metabolite 6-ketoprostaglandin F1 alpha (63.1 +/- 11.3 ng/ml, n = 11, mean +/- SEM), and of prostaglandin E2 (7.0 +/- 0.9 ng/ml, n = 11). This pericardial solution blunted SS-induced increase in mean arterial blood pressure and reduced the prevalence of ventricular fibrillation during reperfusion (six dogs to one dog, p less than 0.05). Blood flow to the ischemic myocardium remained unaffected. Indomethacin, when added to the solution (3 micrograms/ml), reversed the effects of prostaglandin release and arrhythmia development. These data indicate that efferent sympathetic stimulation during a coronary occlusion and reperfusion sequence increases the prevalence of reperfusion-induced ventricular fibrillation that is reduced by pericardial biosynthesis of prostaglandins. Pericardial prostaglandin synthesis may serve as a unique antiarrhythmic function by regulating efferent cardiac sympathetic nerve effects.
Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Español para el Seguimiento del Injerto Coronario (GESIC)
Authors: Sanz G , Pajarón A , Alegría E , Coello I , Cardona M , Fournier J A , Gómez-Recio M , Ruano J , Hidalgo R , Medina A
Published: June 2011

To analyze the efficacy of low-dose aspirin in preventing early aortocoronary vein graft occlusion, 1,112 consecutive patients were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial comparing 50 mg t.i.d. aspirin, 50 mg aspirin plus 75 mg t.i.d. dipyridamole, and placebo. All patients received 100 mg q.i.d. dipyridamole for 48 hours before surgery, and assigned treatment was started 7 hours after surgery. Vein graft angiography was performed in 927 patients (83%) within 28 days of surgery (mean, 10 days). Aspirin plus dipyridamole significantly (p = 0.017) reduced the occlusion rate of distal anastomoses from 18% (placebo) to 12.9%. Occlusion rate in the aspirin group was 14%, which approached statistical significance (p = 0.058). Furthermore, only aspirin plus dipyridamole reduced (p = 0.01) the number of patients with occluded grafts (placebo, 33%; aspirin, 27.1%; aspirin plus dipyridamole, 24.3%). Mediastinal drainage was slightly higher (p = 0.04) in the aspirin plus dipyridamole group (713 +/- 456 ml) than in the other two groups (placebo, 670 +/- 437 ml; aspirin, 629 +/- 337 ml), but hospital mortality (average, 4.6%) and early reoperation (average, 3.9%) rates were similar among the three groups. Thus, low-dose aspirin plus dipyridamole safely improves early saphenous vein aortocoronary graft patency; this effect is an added benefit to a preoperative regimen of dipyridamole.
Incidence of sudden cardiac death associated with coronary artery occlusion in dogs with hypertension and left ventricular hypertrophy is reduced by chronic beta-adrenergic blockade.
Authors: Dellsperger K C , Martins J B , Clothier J L , Marcus M L
Published: June 2011

Because beta-adrenergic blockade has as one of its many effects altered electrophysiological abnormalities after dogs with left ventricular hypertrophy have been subjected to coronary occlusion, we tested the hypothesis that metoprolol (200-400 mg/day) would reduce mortality rates in dogs with one-kidney, one clip left ventricular hypertrophy while a similar reduction in arterial pressure with enalapril (20-40 mg/day) would not. Dogs with left ventricular hypertrophy were given metoprolol or enalapril for 5-7 days before a 3-hour coronary occlusion. Infarct size and risk area were measured with triphenyltetrazolium chloride stain and barium angiography, respectively. For control (n = 15), left ventricular hypertrophy (n = 17), left ventricular hypertrophy plus metoprolol (n = 12), and left ventricular hypertrophy plus enalapril (n = 15) groups, mean arterial pressure, ratio of infarct size to risk area, and dogs experiencing sudden death were 110 +/- 4, 142 +/- 4, 121 +/- 7, and 120 +/- 3 mm Hg; 44 +/- 5%, 65 +/- 5%, 44 +/- 7%, and 30 +/- 4%; and 27%, 65%, 17%, and 53%, respectively. Thus, the excessive increase in early mortality occurring when dogs with hypertension and left ventricular hypertrophy undergo coronary occlusion is interrupted with beta-blockade, possibly via electrophysiological effects rather than by changes in arterial pressure or infarct size.