bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of the frequency- and voltage-dependent effects of quinidine when administered in combination with tocainide in canine Purkinje fibers.
Authors: Valois M , Sasyniuk B I
Published: June 2011

Frequency- and voltage-dependent modification of drug-induced inhibition of maximal upstroke velocity of the action potential (Vmax) by the combined administration of two class I antiarrhythmic drugs was studied in canine Purkinje fibers, taking depression of upstroke velocity as an indicator of sodium channel blockade. The kinetics of onset of drug-induced Vmax depression and the time course of Vmax recovery were studied after exposure to therapeutic concentrations of tocainide (50 microM) and quinidine (5 microM) both singly and in combination. The rate constant for onset of block during a drive train at a cycle length of 600 msec was 0.95 +/- 0.32 pulses in the presence of tocainide and 5.61 +/- 0.50 pulses in the presence of quinidine. The magnitude of block was three times greater with quinidine than with tocainide. The magnitude of block produced by the combination was no greater than that produced by quinidine alone and may be partly due to abbreviation of action potential duration by tocainide. Onset of block in the presence of the combination was best fitted by a double exponential with rate constants of 0.88 +/- 0.19 and 6.47 +/- 1.36 pulses. Vmax recovery after termination of a rapid train of impulses was delayed by both drugs. Poststimulation recovery from either tocainide- or quinidine-induced block was characterized by a single time constant (1.04 +/- 0.49 and 4.81 +/- 0.76 sec, respectively), while that of the combination was characterized by two time constants (0.43 +/- 0.22 and 5.94 +/- 0.56 sec), presumably corresponding to dissociation of each drug from the sodium channel receptor. The mixture of the two drugs produced a large depression of Vmax of early diastolic premature responses without producing much further depression of Vmax than that produced by quinidine alone at longer coupling intervals. The time constant of recovery from tocainide-induced block was greatly dependent upon membrane potential. After steady-state changes in frequency, the combination produced a greater depression of Vmax at rapid heart rates compared with that produced by quinidine alone, but abbreviated action potential duration more at slower heart rates. Addition of tocainide to fibers equilibrated with quinidine shifted the Vmax-membrane potential relationship to more hyperpolarized potentials, resulting in greater depression of Vmax at more depolarized membrane potentials with little or no additional depression of Vmax at more negative membrane potentials. The results provide a rationale for a possible enhanced antiarrhythmic efficacy of a combination of two class I drugs that have different kinetics of interaction with the sodium channel.
Current pharmacologic treatment of elevated serum cholesterol.
Authors: Tikkanen M J , Nikkilä E A
Published: June 2011

A basic difference between dietary and drug therapy of hypercholesterolemia is that dietary therapy can be used as part of a population strategy, whereas the decision to use drugs is always made on an individual basis. In each case, the decision to treat must be based on the assumption that more good than harm is caused to the patient. This is a difficult situation for the physician. As long as there is no easy way of assessing the state and rate of progression of coronary lesions, the physician must treat the patient on statistical grounds only, i.e., rely on the results of studies showing that lowering serum cholesterol significantly decreases the risk of coronary events. Such evidence has recently been strengthened, which increases motivation for both physician and patients. The current general opinion is that drug therapy must be generally confined to those at high risk, i.e., patients with severe hypercholesterolemia. For individuals with moderately elevated serum cholesterol levels, dietary advice and correction of other risk factors should be adequate.
Incidence of early tolerance to hemodynamic effects of continuous infusion of nitroglycerin in patients with coronary artery disease and heart failure.
Authors: Elkayam U , Kulick D , McIntosh N , Roth A , Hsueh W , Rahimtoola S H
Published: June 2011

Sustained therapy with nitroglycerin (NTG) has been reported to provoke the development of early tolerance. Because continuous intravenous NTG infusion is commonly used in patients with coronary artery disease and heart failure, we evaluated the incidence of early tolerance developed within the first 24 hr of therapy in 31 responders to NTG. After documentation of response to NTG, defined as a 10 mm Hg or greater or a 30% or greater reduction in mean pulmonary arterial wedge pressure (PAWP), 16 patients were blindly, randomly assigned to receive placebo and 15 patients were continued on same-dose NTG. Both groups showed an identical fall in PAWP at peak NTG titration (11 +/- 4 mm Hg). Discontinuation of NTG in the placebo group resulted in a rapid increase in PAWP to levels not significantly different from baseline (19 +/- 5 mm Hg at 2 hr vs 23 +/- 6 mm Hg at baseline; p = NS). In the NTG group, PAWP fell from 27 +/- 9 to 14 +/- 7 mm Hg, was 16 +/- 9 mm Hg at 2 hr (p less than .05 vs baseline), and continued to be significantly lower than baseline for 8 hr; however, due to attenuation of effect, PAWP values at 12, 20, and 24 hr were not significantly different from placebo or baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)
Continuous-wave Doppler velocities and gradients across fixed tunnel obstructions: studies in vitro and in vivo.
Authors: Yoganathan A P , Valdes-Cruz L M , Schmidt-Dohna J , Jimoh A , Berry C , Tamura T , Sahn D J
Published: June 2011

The simplified Bernoulli relationship appears to be quite accurate for predicting gradients across discrete valvular obstructions. Controversy exists about how accurately it predicts the severity of disease in longer segment obstructions. In this study we constructed a pulsatile model of subvalvular pulmonary stensosis in vitro to study nine custom-made subvalvular tunnels 2, 4, and 7 mm in length with flow cross sections of 0.5 to 1.5 cm2 and with the stenotic segment proximal to a nonstenotic bioprosthetic valve, and a pulsatile model in vitro of a 16 mm long tunnel-like ventricular septal defect (VSD) of varying cross-sectional area (0.20 to 0.64 cm2). We also compared the observations in vitro with those in an open-chest dog preparation with a tunnel-like interventricular communication. In the subpulmonic stenosis model, for each individual tunnel, 10 instantaneous peak gradients between 15 to 105 mm Hg were available. The pressure gradients across the tunnel alone, measured in the subvalvular area, were consistently higher than the measured gradients across the tunnel plus valve, suggesting some relaminarization of flow (i.e., a decrease in velocity) and pressure recovery (i.e., an increase in pressure) distal to the obstruction. Continuous-wave Doppler velocities across the 4 and 7 mm tunnels for the highest gradients were slightly lower than for the 2 mm tunnel at the same gradients, and it was only for the 0.5 cm2 cross section, 4 and 7 mm tunnels that there was a suggestion of minor viscous energy loss. For all the subvalvular tunnels studied, the Bernoulli relationship accurately predicted the results of the pressure drop across the tunnel only, while the gradient across tunnel plus valve was consistently lower. For the VSD tunnel model in vitro, the Doppler-derived gradients were approximately 40% higher than the measured gradients. The findings for the subvalvular and VSD tunnels in vitro and similar findings in the open-chest dogs with VSD suggest that relaminarization of flow and recovery of pressure occurred distal to the tunnel orifice, whereas continuous-wave Doppler findings correlate with the highest instantaneous gradients measured in the lowest pressure areas at the vena contracta of the tunnel.
Effect of atrial natriuretic factor on transmural myocardial blood flow distribution in the dog.
Authors: Bauman R P , Rembert J C , Himmelstein S I , Klotman P E , Greenfield J C
Published: June 2011

These studies were designed to define the effect of atrial natriuretic peptide (ANP) on coronary flow. ANP was infused as a bolus directly into the left circumflex coronary artery in doses ranging from 0.05 to 5 micrograms in nine open-chest, anesthetized dogs. Coronary flow was measured with an electromagnetic flowmeter. Regional transmural myocardial blood flow and distribution were measured with 11.3 +/- 0.25 micron radionuclide-labeled microspheres. No significant change was noted in systemic hemodynamics (heart rate, arterial pressure, left atrial pressure, or cardiac output) during the course of the studies. ANP produced a transient vasodilatation of coronary resistance vessels and increased flow by 41% after both the 2.5 and 5 micrograms doses. The vasodilatation occurred uniformly throughout the ventricular wall so that the endocardial/epicardial flow ratio remained constant. There was no evidence of coronary vasoconstriction. The peak vasodilatation response occurred 28 +/- 7 sec after the beginning of the infusion of ANP and lasted approximately 3 min. These data support the hypothesis that ANP administration is associated with a vasodilator response in the coronary resistance vessels that may be modulated through either the release of another vasodilator substance or another mechanism.
The long-term effect of oral and percutaneous estradiol on plasma renin substrate and blood pressure.
Authors: Hassager C , Riis B J , Strøm V , Guyene T T , Christiansen C
Published: June 2011

The long-term effect of percutaneous and oral estrogen replacement therapy on blood pressure, plasma renin substrate, and serum estrogens was examined in a 2 year placebo-controlled study with 110 early postmenopausal women. The women were allocated to four treatment groups: (1) oral cyclical combination of 2 mg estradiol valerate and cyproterone acetate, (2) oral placebo, (3) percutaneous 17 beta-estradiol, supplemented by 200 mg oral progesterone during the second year, or (4) percutaneous placebo cream. Systolic and diastolic blood pressure remained unchanged in both hormone treatment groups, whereas the diastolic blood pressure tended to increase in both placebo groups. Plasma renin substrate increased during oral treatment with estradiol, but remained unchanged with percutaneous estradiol. No correlation was found between blood pressure and plasma renin substrate. During percutaneous administration of estradiol, the serum concentrations of estrone and estradiol continued to rise after 3 months and reached a plateau at 6 months of therapy. Serum estrone but not estradiol showed the same pattern during oral estradiol therapy. No further changes in any of the measured variables were observed in the women treated with percutaneous estradiol after addition of cyclical oral progesterone. We conclude that both oral and percutaneous treatment with estradiol may provide protection against the age-related increase in diastolic blood pressure observed in early postmenopausal women, and that the metabolic steady state is not attained until after 3 months of estradiol therapy.
Pericardial effusion causes interstitial pulmonary edema in dogs.
Authors: Sznajder J I , Evander E , Pollak E R , Becker C , Little A G
Published: June 2011

The pulmonary effects of pericardial effusion were studied in eight anesthetized dogs, with emphasis on lung mechanics, O2 exchange, and extravascular thermal lung volume (ETV) accumulation, while warm saline was instilled into the pericardium to elevate pericardial pressure. The results were compared with those from four time-controlled and sham-operated dogs. ETV, as measured by a double-indicator technique, increased from 8.1 +/- 0.8 ml/kg at a pericardial pressure of 0 mm Hg to 12.9 +/- 2.1 ml/kg at 11.0 mm Hg (p less than .01). In the control group, ETV increased from 6.5 +/- 0.7 to 8.2 +/- 0.5 ml/kg over an equal time span. This increase in ETV in the experimental dogs was inversely related to pulmonary compliance, which decreased by 29% as ETV increased (p less than .05), whereas in the time-controlled group of animals it decreased by 8.8%. Arterial PO2 did not deteriorate during the protocol in either group. Histologic examination showed increased interstitial fluid, but neither alveolar fluid nor septal edema, and gravimetric measurements of lung liquid were also consistent with interstitial fluid accumulation in experimental but not control animals. These findings are concordant with the clinical observation that alveolar edema is rarely seen in the presence of pericardial tamponade. Conceivably, progression from interstitial to alveolar edema did not occur both because of the low pulmonary blood flow that occurs as part of pericardial tamponade physiology and/or because the hydrostatic pressures were not elevated enough to produce higher rates of fluid transudation.
Hormonal responses to cardiac tamponade: inhibition of release of atrial natriuretic factor despite elevation of atrial pressures.
Authors: Mancini G B , McGillem M J , Bates E R , Weder A B , DeBoe S F , Grekin R J
Published: June 2011

Atrial distension, rather than change in intra-atrial pressure, has been suggested as a principal mediator of release of atrial natriuretic factor (ANF). During cardiac tamponade, atrial pressures rise whereas transmural pressures and atrial stretch may not be affected. The roles of atrial pressure and atrial distension were investigated in six open-chest dogs subjected to cardiac tamponade and rapid volume expansion as disparate means of affecting intra-atrial pressures and atrial stretch. Hemodynamic measurements, immunoreactive ANF (ir-ANF), plasma renin activity, antidiuretic hormone, epinephrine, and norepinephrine were monitored before, during, and after three interventions: (1) tamponade, (2) rapid volume loading followed by tamponade, and (3) volume loading during tamponade. Volume expansion increased right atrial pressure and caused a significant rise in ir-ANF. Elevations of right atrial pressure caused by tamponade were comparable to those induced by volume infusion, but an increase in ir-ANF was not elicited during tamponade, and the ir-ANF response to volume loading was abolished when performed during tamponade. The relation between the change in ANF concentration and change in right atrial pressure were highly significant in the absence of tamponade, when atrial stretch was freely responsive to volume expansion (r = .73, p less than .0001), but not when stretch was inhibited (r = -.16, p = NS). These observations underscore the importance of considering the modulating effects of atrial compliance, transmural pressure, and atrial stretch on the relation between atrial pressures and ANF release.
Salutary action of nicorandil, a new antianginal drug, on myocardial metabolism during ischemia and on postischemic function in a canine preparation of brief, repetitive coronary artery occlusions: comparison with isosorbide dinitrate.
Authors: Pieper G M , Gross G J
Published: June 2011

The effects of two antianginal drugs, nicorandil and isosorbide dinitrate (ISDN), on metabolism and function of the ischemic myocardium were studied in a preparation of multiple coronary occlusions in barbital-anesthetized dogs. The preparation consisted of three 5 min occlusions of the left anterior descending coronary artery interspersed by 30 min of reperfusion. An equihypotensive dose of nicorandil (7.5 micrograms/kg/min) or ISDN (12.5 micrograms/kg/min) was infused 15 min before and during the second occlusion period. Hemodynamics, myocardial segment shortening (%SS), tissue blood flow, and myocardial oxygen consumption were determined throughout. Uptake of free fatty acids (FFA), glucose, and lactate were determined during control and ischemic periods. At the end of the final 30 min reperfusion period, biopsy samples of transmural tissue were taken for analysis of phosphocreatine, adenine nucleotides, and total tissue water content. No major hemodynamic changes were produced by either drug except for a 5 to 10 mm Hg decrease in mean aortic pressure. Compared with untreated and ISDN-treated hearts, hearts of dogs treated with nicorandil exhibited reversal of a significant increase in FFA uptake during recurrent ischemia. This was accompanied by an attenuation of the increase in oxygen extraction and CO2 production in the ischemic zone by nicorandil, but not by ISDN. Nicorandil, but not ISDN, improved %SS during reperfusion. Endocardial ATP and total adenine nucleotides were preserved in both nicorandil- and ISDN-treated hearts. Tissue edema was also attenuated by both compounds. Thus, nicorandil improved both function and metabolism during recurrent myocardial ischemia independent of a hemodynamic effect, whereas ISDN only attenuated the loss of adenine nucleotides and increase in tissue water.
Cooperative mediation by serotonin S2 and thromboxane A2/prostaglandin H2 receptor activation of cyclic flow variations in dogs with severe coronary artery stenoses.
Authors: Ashton J H , Ogletree M L , Michel I M , Golino P , McNatt J M , Taylor A L , Raheja S , Schmitz J , Buja L M , Campbell W B
Published: June 2011

We have reported previously that thromboxane A2/prostaglandin (PG)H2 and serotonin independently mediate the occurrence of cyclic flow variations (CFVs) in a canine preparation of severe coronary artery narrowing. This may be due to an effect of these substances on platelets and/or the vascular wall. We tested the hypothesis that there is a cooperative effect between thromboxane A2/PGH2 and serotonin receptor stimulation in the development of CFVs in this animal preparation. After placement of a hard plastic cylindrical constrictor around the left anterior descending coronary artery, CFVs develop and are characterized by repetitive cycles of declines in coronary blood flow and abrupt increases in flow. In a control group of dogs, CFV frequency (cycles/hour) and severity (lowest coronary blood flow just before its restoration) did not change significantly over a 3 hr interval. In a second group of dogs, CFVs were established after constrictor placement, abolished with the serotonin (5HT2) receptor antagonist ketanserin, and reestablished by the continuous infusion of serotonin into the left atrium. Serotonin-induced CFVs were then abolished with a thromboxane A2/PGH2 receptor antagonist, SQ29,548, or a thromboxane synthetase inhibitor, dazoxiben (UK37,248). The relative specificity of the respective antagonists, SQ29,548 and ketanserin, was determined in canine platelets and rat aortic vascular strips. No significant cross-reactivity between ketanserin and SQ29,548 was found. Thus, the data obtained in these studies demonstrate a cooperative interaction between thromboxane A2/PGH2 and serotonin S2 receptors that contributes to the development of CFVs in this experimental preparation.
Circus movement in the canine atrium around the tricuspid ring during experimental atrial flutter and during reentry in vitro.
Authors: Frame L H , Page R L , Boyden P A , Fenoglio J J , Hoffman B F
Published: June 2011

A Y-shaped lesion in the right atrium allows induction of atrial flutter in dogs. We recorded the activation sequence during this tachycardia from 96 endocardial bipolar electrodes using intracavitary electrode arrays during 12 separate episodes in three isolated perfused hearts. In each case a reentrant impulse circulated around the tricuspid valve orifice in either a clockwise or counter-clockwise direction. Cutting the pathway terminated the rhythm and prevented its reinduction. There was no discrete segment of markedly slow conduction in the reentrant circuit. The tachycardia cycle length was decreased by methacholine and increased by lidocaine. Reentry was also induced in atrial tissue around the tricuspid orifice when this structure was isolated and superfused in vitro. Tachycardia cycle lengths varied from 205 to 399 msec, depending on the circumference of the ring and temperature. Induction of tachycardia by premature stimulation depended on differences in the duration of the effective refractory period among parts of the ring. Conduction velocity was relatively uniform and was slower during tachycardias than during pacing at long cycle lengths. Analysis of the response to premature stimuli that reset the tachycardia provided evidence for incomplete recovery of excitability between depolarizations during the tachycardia. Fast-response action potentials were recorded throughout the pathway and up to six to eight cell layers deep. Histologic studies showed the supravalvular lamina, a circumferential band of fibers several cell layers below the endocardial surface, to be continuous around the tricuspid orifice. Propagation through this layer best explains the conduction velocities observed in the intact heart during flutter in this preparation.
Transseptal pressure gradient and diastolic ventricular septal motion in patients with mitral stenosis.
Authors: Thompson C R , Kingma I , MacDonald R P , Belenkie I , Tyberg J V , Smith E R
Published: June 2011

Previous studies from our laboratory have shown that the position of the ventricular septum relative to the two ventricles at end-diastole is determined by the instantaneous transseptal pressure gradient (TSG) defined as left ventricular minus simultaneous right ventricular pressure. Since patients with mitral stenosis often have exaggerated leftward (paradoxic) motion of the ventricular septum during early diastole, we studied seven patients with mitral stenosis undergoing cardiac catheterization to determine if position (and therefore motion) of the ventricular septum was determined by TSG throughout diastole. M Mode echocardiograms derived from a two-dimensional parasternal short-axis view were recorded with simultaneous micromanometer measurements of left ventricular and right ventricular pressures. Six of seven patients demonstrated abnormal early diastolic leftward motion of the ventricular septum in at least one cardiac cycle. TSG measured at intervals throughout diastole ranged from -2.5 to +20 mm Hg, with abnormal TSG observed in most of the 40 cardiac cycles selected for analysis. The intracardiac position of the ventricular septum, defined as the distance from the right ventricular epicardium (RVEpi) to the left surface of the ventricular septum normalized for total cardiac dimension (RVEpi-VS), was plotted against left ventricular pressure, right ventricular pressure, and TSG. Linear regression of pooled data from all patients (164 observations) demonstrated a highly significant correlation between the instantaneous TSG and the relative intracardiac position of the ventricular septum (RVEpi-VS = 1.52 TSG + 42.7; r = .79, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative relationship between left ventricular function and serum cardiac myosin light chain I levels after coronary reperfusion in patients with acute myocardial infarction.
Authors: Isobe M , Nagai R , Ueda S , Tsuchimochi H , Nakaoka H , Takaku F , Yamaguchi T , Machii K , Nobuyoshi M , Yazaki Y
Published: June 2011

To estimate the extent of myocardial infarction after coronary artery reperfusion, serum levels of cardiac myosin light chain (LC) I and creatine kinase (CK) were determined serially in 49 patients with acute myocardial infarction. Intracoronary thrombolysis was successful in 25 patients (reperfusion group), and 24 patients were treated in a conventional manner (control group). The peak level of CK appeared significantly earlier in the reperfusion group (11.3 +/- 3.1 hr, mean +/- SD) than in the control group (21.6 +/- 7.2 hr). Cumulative release of CK was significantly related to angiographically determined left ventricular ejection fraction 1 month after the attack in both groups (r = -.50; -.45, respectively). However, the amount of cumulative release of CK in the reperfusion group was greater compared with that in those with the same left ventricular ejection fraction in the control group. Peak appearance time of LCI was almost equal in the two groups (3.8 +/- 1.4 vs 3.9 +/- 1.2 days). Peak levels of LCI were related to the left ventricular ejection fraction in the reperfusion group (r = -.63) and in the control group (r = -.74), and the slopes of their regression lines were similar. The cardiac index obtained on the day of onset in the two groups was related to peak levels of LCI but not to total release of CK. These results suggest that serum levels of LCI reflect the changes in left ventricular function after acute myocardial infarction, regardless of the presence of coronary reperfusion. Thus, serial determinations of LCI in serum facilitate noninvasive assessment of the effects of intracoronary thrombolysis on infarct size.
Double-blind crossover comparison of enoximone and placebo in patients with congestive heart failure.
Authors: Choraria S K , Taylor D , Pilcher J
Published: June 2011

The efficacy of oral enoximone, a new positive inotropic and vasodilator agent, was assessed in 12 patients with chronic congestive heart failure (New York Heart Association [NYHA] class II or III) in a double-blind randomized crossover comparison with placebo. Duration of each treatment was 6 weeks and the dose of enoximone was 150 mg tid. Efficacy was assessed by exercise tolerance, symptoms, radionuclide angiography for ejection fraction at rest and during exercise, and Holter monitoring. Two patients were withdrawn before completion of the study, one with pulmonary edema after 1 week on placebo and the other for noncompliance with enoximone therapy. Symptom-limited exercise capacity improved with enoximone by 30% and 43% (p less than .01) compared with baseline after 2 and 6 weeks treatment, respectively. Ejection fraction improved at rest (p less than .02) with enoximone but not with placebo. No change was found during exercise. Heart rate and blood pressure remained unaltered. During treatment with enoximone symptoms of exertional dyspnea and fatigue were improved and NYHA class decreased by at least one class for every patient. Holter monitoring revealed an overall increase (NS) in ectopic activity during enoximone therapy. There were no serious adverse effects and laboratory values did not change significantly. The addition of enoximone to the existing therapy of patients with moderately severe congestive heart failure provided clear and sustained subjective and objective benefit when compared with placebo.
Augmentation of renal blood flow and sodium excretion in hypertensive patients during blood pressure reduction by intravenous administration of the dopamine1 agonist fenoldopam.
Authors: Murphy M B , McCoy C E , Weber R R , Frederickson E D , Douglas F L , Goldberg L I
Published: June 2011

Activation of dopamine1 (DA1) receptors relaxes vascular smooth muscle, especially in the renal vascular bed. Fenoldopam, the first selective DA1-receptor agonist that can be administered to man, was infused intravenously in 17 patients with essential hypertension (mean blood pressure 152/101 mm Hg). It reduced blood pressure in a dose-dependent fashion at doses between 0.025 and 0.5 microgram/kg/min and the antihypertensive effect was sustained during 2 hr infusions. In 10 patients studied during free-water diuresis, fenoldopam increased renal plasma flow by 42%, glomerular filtration rate by 6%, and sodium excretion by 202%, while lowering mean arterial pressure by 12% (all p less than .05). Similar promotion of sodium excretion was observed during blood pressure reduction in six additional patients studied without water loading. Pronounced enhancement of renal function in spite of blood pressure reduction suggests that fenoldopam might have a special role in the treatment of patients with hypertension and renal impairment.
Surgical ablation of ventricular tachycardia with sequential map-guided subendocardial resection: electrophysiologic assessment and long-term follow-up.
Authors: Haines D E , Lerman B B , Kron I L , DiMarco J P
Published: June 2011

A new operative technique of sequential map-guided subendocardial resection (SER) was used in 45 consecutive patients for the treatment of sustained ventricular tachycardia due to coronary artery disease. This technique is characterized by map-guided SER or cryothermic ablation during normothermic cardiopulmonary bypass, followed by repeated sequences of programmed stimulation to assess adequacy of resection. The patients' mean age was 59 +/- 10 years and the mean left ventricular ejection fraction was 34 +/- 12%. Twenty-five (56%) patients had a history of myocardial infarction within the previous 2 months. After ventriculotomy, 34 patients (76%) had inducible monomorphic ventricular tachycardia. These patients underwent repeated sequences of ventricular tachycardia induction and mapping during normothermic bypass followed by successive SER or cryothermic ablation until sustained monomorphic ventricular tachycardia was no longer inducible. Twenty-seven patients had a total of 60 discrete, mappable tachycardias induced and seven patients had 10 discrete tachycardias that were too fast to accurately map. In the remaining 11 patients, no ventricular tachycardia was inducible after ventriculotomy and SER, which included all visually identifiable scar, was performed. The mean cardiopulmonary bypass time was 102 +/- 27 min. Forty-one of 45 patients (91%) survived to hospital discharge, and 35 of 41 patients (85%) had no inducible ventricular tachycardia at postoperative electrophysiologic evaluation performed in the absence of all antiarrhythmic drugs. The remaining six patients had no inducible ventricular tachycardia with drug therapy. All four operative nonsurvivors had refractory cardiac collapse preoperatively. Over 19 +/- 12 months of follow-up, there were four sudden cardiac deaths and no nonfatal recurrences of ventricular tachycardia. There were seven additional cardiac deaths. Actuarial cardiac survival was 0.57, and freedom from arrhythmic events was 0.76 at 42 months. Thus, in the absence of cardiogenic shock, the technique of sequential map-guided SER achieves: (1) a high operative survival with acceptable perfusion times, (2) excellent long-term arrhythmia control, and (3) survival comparable to that in patients with similar left ventricular function and no history of ventricular tachyarrhythmia.
Antibiotic prophylaxis of experimental endocarditis after dental extractions.
Authors: Malinverni R , Overholser C D , Bille J , Glauser M P
Published: June 2011

In rats with catheter-induced sterile aortic valve vegetations we studied the efficacy of single-dose amoxicillin and single-dose erythromycin prophylaxis for the prevention of bacterial endocarditis after extractions of periodontally diseased teeth. Endocarditis after extractions occurred in 89% of control animals and was due to group G streptococci, to Staphylococcus aureus, or to both organisms. A single-dose of amoxicillin or erythromycin successfully prevented endocarditis due to these bacterial species. The analysis of the bacteremia (by culturing blood drawn 1 min after extraction on penicillinase-containing blood agar plates) indicated that amoxicillin did not influence the incidence or the magnitude of circulating group G streptococci and S. aureus, while erythromycin apparently suppressed them. However, when care was taken to eliminate blood erythromycin by a lysis-centrifugation process, the incidence and magnitude of bacteremia after erythromycin prophylaxis was similar to that in control rats. We conclude that single doses of amoxicillin and erythromycin successfully prevent experimental endocarditis after dental extractions. Since this prophylaxis was operative by mechanisms other than the prevention of the circulation of bacteria before seeding the valvular vegetations, it suggests that recommendations for prevention of bacterial endocarditis should not be aimed only at providing adequate antibiotic blood levels to suppress the bacteremia produced by the invasive procedure.
Value and limitations of Doppler echocardiography in the quantification of stenotic mitral valve area: comparison of the pressure half-time and the continuity equation methods.
Authors: Nakatani S , Masuyama T , Kodama K , Kitabatake A , Fujii K , Kamada T
Published: June 2011

Two Doppler methods, the pressure half-time method proposed by Hatle and the method based on the equation of continuity, were used to estimate stenotic mitral valve area noninvasively, and the accuracy of these methods was examined in patients with and without associated aortic regurgitation. Mitral valve area determined at catheterization by the Gorlin formula was used as a standard of reference. The study population consisted of 41 patients with mitral stenosis, and 20 of the 41 patients had associated aortic regurgitation. According to the equation of continuity, mitral valve area was determined as a product of aortic or pulmonic annular cross-sectional area and the ratio of time velocity integral of aortic or pulmonic flow to that of the mitral stenotic jet. Mitral valve area was determined by the pressure half-time method as 220/pressure half-time, the time from the peak transmitral velocity to one-half the square root of the peak velocity on the continuous-wave Doppler-determined transmitral flow velocity pattern. The pressure half-time method tended to overestimate catheterization measurements, and the correlation coefficient for this relation was .69 (SEE = 0.44 cm2). The correlation coefficient improved to .90 when the patients with associated aortic regurgitation were excluded. Mitral valve areas determined by the continuity equation method correlated well with catheterization measurements at a correlation coefficient of .91 (SEE = 0.24 cm2), irrespective of the presence of aortic regurgitation. The ratio of the time-velocity integral or aortic or pulmonic flow to the time-velocity integral of mitral stenotic jet also correlated well with mitral valve area determined by catheterization at a correlation coefficient of .84 (SEE = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)
Prevalence of ischemic resting and stress electrocardiographic abnormalities and angina among 40- to 59-year-old men in selected U.S. and U.S.S.R. populations.
Authors: Abernathy J R , Thorn M D , Trobaugh G B , Ekelund L G , Maciolowski M , Lupovetsky B , Shelnova S , Zhukovsky G , Shestov D , Deev A
Published: June 2011

The prevalence of electrocardiographic (ECG) abnormalities and angina was investigated in 40- to 59-year-old men from two samples, one from a U.S.S.R. study in two locations and one from a U.S. study in nine locations. ECG abnormalities were defined by the Minnesota code and angina was defined by the Rose questionnaire. No differences were found in the prevalence of major Q waves and major or minor ischemia between the two samples, but differences were found in specific indicators of major ischemia. Major ischemic changes were more prevalent in older subjects in both samples. Estimated prevalence of angina was 50% less in the U.S. sample than in the U.S.S.R. sample, and this was consistent with the proportion of subjects excluded from the exercise test because of angina. In both samples, subjects with ECG abnormalities had higher systolic blood pressures. No difference in exercise test abnormalities was found between samples; however, more subjects with a history compatible with coronary artery disease were excluded from the U.S.S.R. sample.
Direct myocardial and coronary effects of enalaprilat in patients with dilated cardiomyopathy: assessment by a bilateral intracoronary infusion technique.
Authors: Foult J M , Tavolaro O , Antony I , Nitenberg A
Published: June 2011

Angiotensin II elicits contractile responses in the coronary arteries and myocardial tissue, which suggests that blockade of the renin-angiotensin system by specific agents should lead to both coronary vasodilation and an alteration of left ventricular inotropism. The present work was designed to delineate--independently from its systemic effects--the intrinsic actions of an angiotensin converting-enzyme inhibitor on the coronary circulation and left ventricular function. To minimize peripheral effects, a bilateral intracoronary infusion of enalaprilat (0.05 mg.min-1, 1 ml.min-1 in each coronary artery) was performed in 16 patients with dilated cardiomyopathy. All patients had normal coronary arteriograms. In 12 patients (group I) the intracoronary infusion of enalaprilat resulted in minimal peripheral changes, with a 5% reduction in the mean aortic pressure (p less than .05) and no significant alteration in indexes of preload, i.e., left ventricular end-diastolic pressure and volume, or of afterload, i.e., left ventricular end-systolic stress and systemic resistances. Myocardial oxygen consumption was also unaffected by the intracoronary infusion of enalaprilat. Coronary vasodilation was demonstrated by a significant elevation of coronary sinus blood flow (+19%, from 181 +/- 73 to 214 +/- 79 ml.min-1, p less than .001) and a reduction of coronary resistance (-18%, from 0.51 +/- 0.17 to 0.41 +/- 0.15 mm Hg.ml-1.min, p less than .001), with a parallel increase in coronary sinus oxygen content and pressure (both p less than .05). Oxygen extraction by the myocardium was reduced (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Antiarrhythmic activity, electrocardiographic effects and pharmacokinetics of the encainide metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide in man.
Authors: Barbey J T , Thompson K A , Echt D S , Woosley R L , Roden D M
Published: June 2011

Although encainide is an effective antiarrhythmic agent, plasma concentrations and pharmacologic effects are not well correlated. One explanation is the generation of active metabolites: while in most patients (extensive metabolizers; EMs) concentrations of the metabolites O-desmethyl encainide (ODE) and 3-methoxy-O-desmethyl encainide (3MODE) are higher than those of encainide, a small subset (poor metabolizers; PMs) lack the ability to extensively biotransform encainide. Considerable data from studies in vitro and animal studies, as well as indirect evidence in patients, indicate that ODE and 3MODE produce the effects seen during long-term encainide therapy in EMs. We now report the initial direct evaluation of the pharmacologic actions of these metabolites of encainide in man. Nine patients with ventricular arrhythmias, seven of the EM phenotype and two of the PM phenotype, were studied. Chronic high-frequency ventricular arrhythmias were suppressed by encainide therapy in seven of nine; monitoring arrhythmia frequency during withdrawal of encainide allowed definition of plasma concentrations of encainide and metabolites associated with arrhythmia suppression. Intravenous infusions of both ODE and 3MODE suppressed chronic ventricular arrhythmias, while infusions of placebo had no effect. ODE clearance was a function of metabolizer phenotype, with higher clearance (mean 914 ml/min; range 554 to 1,314) in EMs than in PMs (434, 298 ml/min); moreover, 3MODE was detected during ODE infusions in all seven EMs but in neither PM. 3MODE clearance was more uniform (mean 289 ml/min in EMs [range 180-410] vs 300 and 78 ml/min in the two PMs) and ODE was not detected in any subject during 3MODE infusion. Encainide itself was not detected after any infusion of ODE or 3MODE. During withdrawal of encainide therapy, ODE plasma concentration at the time of arrhythmia recurrence was 55 +/- 40 ng/ml (mean +/- SD), while ODE by infusion was effective at a concentration of 37 +/- 15 ng/ml. Similarly, plasma concentration of 3MODE at the time of arrhythmia recurrence after withdrawal of chronic encainide was 116 +/- 35 ng/ml and that during 3MODE infusion was 105 +/- 50 ng/ml. While both compounds prolonged QRS duration, ODE was the more potent, increasing QRS by 9.2 +/- 1.6% per 100 ng/ml vs 1.2 +/- 0.5% per 100 ng/ml for 3MODE. On the other hand, 3MODE prolonged the corrected JT interval by 1.9 +/- 0.6% per 100 ng/ml, while ODE shortened it by 2.7 +/- 1.9% per 100 ng/ml.(ABSTRACT TRUNCATED AT 400 WORDS)
Inducible sustained ventricular tachycardia 4 years after experimental canine myocardial infarction: electrophysiologic and anatomic comparisons with early healed infarcts.
Authors: Hanich R F , de Langen C D , Kadish A H , Michelson E L , Levine J H , Spear J F , Moore E N
Published: June 2011

We studied a group of 17 dogs 4 to 6 years after infarction produced by 2 hr occlusion of the anterior descending coronary artery followed by reperfusion. Dogs in this "late" infarct group were compared with a group of 24 dogs with "early" healed infarcts (2 to 24 weeks old). With signal-averaging techniques body surface potentials were recorded during sinus rhythm. After thoracotomy epicardial electrograms were recorded from 45 standardized sites within the infarcted region and characteristics of selected electrograms were compared with anatomic features of underlying myocardium. Epicardial recordings from the late infarct group demonstrated earlier local activation (p less than .001) and shorter electrogram duration (p less than .001) when compared with recordings from the early infarct group. There was less temporal dispersion of activation and electrogram duration among the 45 sites in dogs with late infarcts as measured by respective coefficients of variance (p = .007 and less than .001). With programmed stimulation six dogs in the late and eight in the early infarct group exhibited inducible sustained ventricular tachycardia. Mean cycle length of the tachycardia in dogs with late infarcts was significantly shorter (p = .035). Late potentials were notably less prominent in dogs in the late infarct group with ventricular tachycardia than in dogs in the early infarct group. Fewer abnormal electrophysiologic characteristics of late infarcts coincided with relatively less scar in the underlying myocardium. Moreover, the strength of electrophysiologic-anatomic correlations differed in late as opposed to early infarcts. The latter findings suggest long-term evolution of infarct anatomy. We conclude that a substrate for reentrant tachycardia is present in dogs 4 to 6 years after reperfused infarction. Conduction characteristics are less abnormal in these late healed infarcts and are associated with a shorter ventricular tachycardia cycle length and less pronounced late potentials on the body surface.
Hyperkinesis without the Frank-Starling mechanism in a nonischemic region of acutely ischemic excised canine heart.
Authors: Goto Y , Igarashi Y , Yamada O , Hiramori K , Suga H
Published: June 2011

To determine the essential mechanism of increased systolic wall motion, i.e., hyperkinesis, in a nonischemic region (NIR) during acute ischemia, we simultaneously evaluated global and regional function of the excised, cross-circulated canine left ventricle connected to a volume servo pump before and after coronary occlusion. Regional areas were determined with pairs of orthogonal subendocardial sonomicrometers in the ischemic region (IR) and NIR. After coronary occlusion with left ventricular end-diastolic and stroke volumes kept constant, the amount of systolic area shrinkage (delta A) in NIR increased by 33 +/- 41% (p less than .05), despite a decrease in end-diastolic regional area by 3 +/- 4% (p less than .05). Regional work obtained from the wall tension-regional area (T-A) loop in NIR decreased by 50 +/- 24% due to a similar decrease in afterload despite the presence of hyperkinesis, indicating regional systolic unloading. When left ventricular end-diastolic volume was subsequently increased with a constant stroke volume, delta A in NIR increased at the expense of a further decrease in delta A in IR. The end-systolic T-A relationship in NIR remained unchanged, whereas that in IR markedly shifted rightward, suggesting that the contractile state of NIR was constant. These results indicate that hyperkinesis in NIR during acute ischemia can occur without a utilization of the Frank-Starling mechanism or an enhancement of regional contractile state, and that the essential mechanism of this phenomenon is regional afterload reduction due to an intraventricular mechanical interaction between IR and NIR.
Influence of heart rate, preload, afterload, and inotropic state on myocardial ultrasonic backscatter.
Authors: Sagar K B , Pelc L E , Rhyne T L , Wann L S , Waltier D C
Published: June 2011

Ultrasonic backscatter is substantially modified by pathologic changes in myocardium. Influence of physiologic changes in heart rate, mean arterial pressure, preload, and inotropic state were studied in 17 anesthetized open-chest dogs. Heart rate was changed with atrial pacing/ULFS'49 (a selective bradycardiac agent). Mean arterial pressure was varied with aortic constriction/nitroprusside, preload was altered with nitroglycerin/volume infusion, and inotropic states were altered with dobutamine (10 microns/kg)/esmolol (100 microns/kg). IBR5, an optimum weighted frequency average (4 to 6.8 MHz) of the squared envelope of diffraction corrected for absolute backscatter, and the Fourier coefficient of amplitude modulation (FAM), an index of cardiac cycle-dependent variation, were measured from six sequential electrocardiographically gated intervals throughout the cardiac cycle. Heart rate, mean arterial pressure, preload, and inotropic state did not significantly affect IBR5. FAM increased from 3.5 +/- 0.3 dB (mean +/- SEM) to 7.0 +/- 0.4 dB (p less than .01) at a heart rate of 120 beats/min, and decreased to 3.9 +/- 0.4 at a heart rate of 160 beats/min. No change in FAM was noted with a rise (70 +/- 12 to 45 +/- 10 mmHg) in mean arterial pressure or preload (an increase or decrease in diastolic segment length of +/- 10% from the baseline). Dobutamine produced a significant increase in left ventricular dP/dt (2600 +/- 200 to 3475 +/- 275 mm Hg) and FAM (3.4 +/- 0.1 to 6.4; p less than .01). Esmolol significantly reduced left ventricular dP/dt (2600 +/- 200 to 2000 +/- 175 mm Hg, p less than .05) and FAM (3.4 +/- 0.01 to 6.4 +/- 0.1; p less than .01). We conclude that IBR5 is independent of heart rate, mean arterial pressure, preload, and inotropic state. Cardiac cycle-dependent amplitude modulation follows changes in cardiac contraction.
Differing mechanisms of exercise flow augmentation at the mitral and aortic valves.
Authors: Rassi A , Crawford M H , Richards K L , Miller J F
Published: June 2011

To determine the mechanisms by which blood flow increases across the mitral and aortic valves during exercise, 18 normal men were studied during graded supine and upright bicycle exercise at matched workloads. Mitral valve orifice and ascending aortic blood velocities were recorded by Doppler echocardiography during steady states at each stage of exercise. Parasternal two-dimensional echocardiographic imaging of the ascending aorta adjacent to the aortic valve orifice and the mitral valve orifice at the tips of the valve leaflets was used to calculate changes in cross-sectional area during exercise. Heart rate increased from rest to exercise from 67 to 150 beats/min (124%) during supine exercise and from 72 to 147 beats/min (104%) during upright exercise. Stroke volume increased 20% during supine and 46% during upright exercise; the increase in stroke volume was statistically significant when rest and exercise were compared and when the magnitude of change was compared vs position (p less than .05). The increase in stroke volume measured at the ascending aorta was accomplished by an increase in the velocity-time integral (+15% supine and +48% upright, p less than .05), with little change in aortic cross-sectional area (5% supine and 0% upright, p = NS). By contrast, the increase in flow rate measured at the mitral valve was predominantly due to an increase in mean diastolic cross-sectional area (+29% supine and 34% upright, p less than .05); the velocity-time integral did not increase significantly (-10% supine and 4% upright; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)