bluuebunny/crossref_metadata_2025 huggingface dataset:
Left ventricular pressure-volume relations shift to the left after long-term loss of pericardial restraint.
Authors: Hosenpud J D , Yung N N , Morton M J
Published: June 2011

The short-term effect of pericardiectomy is to shift the in vivo left ventricular (LV) pressure-volume curve to the right. We studied nine weight-matched pairs of male guinea pigs 28 to 39 days (mean 35) after complete pericardiectomy or sham thoracotomy to determine the long-term effects of pericardiectomy on LV pressure-volume relations. Hemodynamic and in vitro LV pressure-volume data were collected in matched pairs on the same day, 2 to 3 hr after catheter placement and recovery from anesthesia. Cardiac output was measured by the microsphere reference sample method. Postsurgical weight gain was similar in both groups: 823 +/- 6 (mean +/- SD) to 925 +/- 6 g in the pericardiectomy group and 829 +/- 7 to 927 +/- 7 g in the sham thoracotomy group. We found no difference in LV weight: 1.555 +/- 0.145 g in the pericardiectomy group vs 1.564 +/- 0.148 g in the sham thoracotomy group, nor any difference in heart rate, mean arterial, right atrial, or left ventricular end-diastolic pressures, cardiac outputs, or stroke volumes (p = NS). LV pressure-volume relations, however, were shifted to the left in the pericardiectomy group (p less than .005). At 10 mm Hg, LV volume in the pericardiectomy group (0.85 +/- 0.22 cc) was less than that in the sham thoracotomy group (1.02 +/- 0.15 cc; p less than .025). The LV stress-elastic modulus relationship was not different between groups (p greater than .30). One month after pericardiectomy, LV pressure-volume relations in vitro were shifted to the left without a change in LV weight, LV elastic modulus, or hemodynamics. We speculate that this shift compensates for the lack of pericardial restraint and returns LV volume and hemodynamics to normal in vivo.
Erythrocyte membrane sodium transport in patients with treated and untreated essential hypertension.
Authors: Cole C H
Published: June 2011

Various parameters of erythrocyte membrane sodium transport were measured in patients with untreated essential hypertension, in the normotensive offspring of parents with hypertension, and in patients whose hypertension had been controlled by medication. Net sodium efflux, measured by an isotopic tracer technique, was 2.12 +/- 0.17 mM Na+/1 of red blood cells (RBCs)/hr in patients with untreated essential hypertension, compared with 1.55 +/- 0.12 mM Na/1 of RBCs/hr in a group of normotensive controls (p less than .025). Partitioning sodium efflux into ouabain-sensitive and ouabain-insensitive components revealed a significant elevation of both components of membrane sodium transport in the patients with untreated essential hypertension. Ouabain-sensitive sodium efflux was 1.38 +/- 0.09 mM Na/1 RBCs/hr in the patients, compared with 1.04 +/- 0.07 mM Na/1 RBCs/hr in the controls. Ouabain-insensitive sodium efflux was also increased from 0.51 +/- 0.05 mM Na/1 RBCs/hr in the controls to 0.74 +/- 0.09 mM Na/1 RBCs/hr in those with untreated hypertension. Despite these changes in sodium efflux, Na,K-ATPase activity in the erythrocyte membrane, measured at maximum velocity (Vmax), was normal, suggesting that the observed abnormalities in membrane sodium transport in patients with untreated essential hypertension resulted from a change in pump control mechanisms rather than a change in enzyme activity. With the techniques used in this study we were unable to identify changes in erythrocyte membrane transport in the normotensive offspring of hypertensive parents. Membrane sodium transport was also examined in hypertensive patients whose blood pressure had been controlled by medication. In this group it was found that erythrocyte sodium transport did not differ from that in our control group, which suggests that treatment of hypertension can modify fundamental pathophysiologic changes at the level of the cell membrane.
Amiodarone: clinical efficacy and toxicity in 96 patients with recurrent, drug-refractory arrhythmias.
Authors: Fogoros R N , Anderson K P , Winkle R A , Swerdlow C D , Mason J W
Published: June 2011

Ninety-six patients with recurrent, drug-refractory tachyarrhythmias were treated with amiodarone for 8.0 +/- 7.5 months (range 1 day to 27 months): 77 for recurrent ventricular tachycardia or ventricular fibrillation (VT/VF), two for complex ventricular ectopy, and 17 for supraventricular tachyarrhythmias. The actuarial incidence of successful amiodarone therapy was 52 +/- 7% at 12 months and 28 +/- 9% at 24 months for patients with VT/VF. Neither patient with complex ventricular ectopy was successfully treated. Among the patients with supraventricular tachyarrhythmias, 64.7% were successfully treated for 7.7 +/- 7.6 months (range 1 to 22 months). Amiodarone toxicity occurred in 66 of 91 patients (72.5%) treated for more than 1 week. Fourteen patients had therapy-limiting toxicity. Of these 14, six had pulmonary toxicity, four had arrhythmia exacerbation, one had hepatitis, one had renal toxicity, one had rash, and one had erythema nodosum. The actuarial incidence of therapy-limiting side effects was 27 +/- 7% at 15 months. We conclude that amiodarone is useful in the treatment of refractory tachyarrhythmias but that the rate of efficacy in VT/VF is lower and the incidence of significant toxicity is higher than has been generally appreciated.
Left ventricular ejection fraction during cardiac surgery: a two-dimensional echocardiographic study.
Authors: Dubroff J M , Clark M B , Wong C Y , Spotnitz A J , Collins R H , Spotnitz H M
Published: June 2011

Although long-term effects have been studied, the immediate effect of surgery for acquired heart disease on left ventricular function is not well defined. Accordingly, 44 adults with acquired heart disease underwent intraoperative two-dimensional echocardiography with a gas-sterilized transducer before and immediately after cardiopulmonary bypass. Ejection fraction was measured by short-axis area change at the maximum left ventricular cross section (SAAC-EF) and also by a method using multiple sections. Correction of both mitral and aortic regurgitation produced a significant intraoperative decrease in ejection fraction from 0.49 +/- 19 (SD) to 0.32 +/- 0.16 (p less than .02) and from 0.41 +/- 0.13 to 0.30 +/- 0.17 (p less than .0005), respectively. Relief of aortic stenosis and mitral stenosis resulted in an intraoperative increase in ejection fraction from 0.45 +/- 0.10 to 0.55 +/- 0.09 (p less than .02) and from 0.41 +/- 0.05 to 0.50 +/- 0.07 (p less than .05), respectively. Ejection fraction after coronary artery bypass grafting was unchanged. Preload (end-diastolic area) was significantly decreased after correction of aortic regurgitation (p less than .02) but unchanged in other lesions. We conclude that (1) correction of pure mitral and aortic valvular lesions produces characteristic alterations in ejection fraction in the immediate postoperative period; (2) with the possible exception of patients with aortic regurgitation, the observed change in ejection fraction does not appear to reflect changes in preload; (3) noninvasive assessment of left ventricular function by two-dimensional echocardiography during cardiac surgery appears feasible and could provide data important for clinical decision making in the early postoperative period.
Measurement of systolic and diastolic flow rates in the coronary artery system by x-ray densitometry.
Authors: Spiller P , Schmiel F K , Pölitz B , Block M , Fermor U , Hackbarth W , Jehle J , Körfer R , Pannek H
Published: June 2011

The reliability of a modified videodensitometric and photodensitometric sampling technique for measuring phasic flow rates in the coronary artery system was examined. Electromagnetic flow measurements were performed in a circulatory model with continuous and pulsatile flow and intraoperatively in aortocoronary bypass grafts; cineangiograms were made simultaneously. Based on the front velocities of injected boluses of contrast medium, the densitometric measurement overestimated the electromagnetically measured flow systematically by about 20%. Systolic and diastolic flow rates in aortocoronary bypass grafts and coronary arteries determined from biplane cineangiograms in 34 patients generally revealed the typical pulsatile flow pattern familiar from electromagnetic and ultrasonic flow measurements. Flow velocities in unstenosed coronary arteries were nearly identical before and after branchings of the vessels, whereas the corresponding flow rates were higher in proximal than in distal segments. The identical flow velocities in different branches of the same vessel and the low variability of this parameter in different patients may be a suitable index of the effect of stenoses on coronary arterial blood flow.
Prediction of the severity of left ventricular outflow tract obstruction by quantitative two-dimensional echocardiographic Doppler studies.
Authors: Lima C O , Sahn D J , Valdes-Cruz L M , Allen H D , Goldberg S J , Grenadier E , Barron J V
Published: June 2011

In this study we explored the use of continuous wave Doppler echocardiography guided by simultaneous two-dimensional echocardiographic imaging as a method for noninvasively estimating pressure gradients in patients with discrete forms of left ventricular outflow tract obstruction. We studied 16 children, ages 6 months to 17 years, with valvular aortic stenosis (n = 12) or with discrete subaortic stenosis (n = 4) and compared maximal Doppler velocities in the aorta with pressure gradients obtained at cardiac catheterization. Examinations could be performed from the suprasternal notch view or from the apical left ventricular outflow tract view with equal accuracy for the study of flow in the left ventricular outflow tract, and results were comparable in both views. With a simplified Bernoulli relationship (gradient = 4 X [maximal velocity]2), results suggested that Doppler echocardiography could be used to predict the severity of obstruction in our patients with a correlation coefficient of r = .94 (SEE +/- 7.5 mm Hg) between Doppler-estimated gradients and gradients obtained at catheterization. The method appears promising for initial evaluation and for serial management of patients with discrete forms of left ventricular outflow tract obstruction.
Electrophysiologic actions of O-demethyl encainide: an active metabolite.
Authors: Duff H J , Dawson A K , Roden D M , Oates J A , Smith R F , Woosley R L
Published: June 2011

Differences between the electrophysiologic actions of the antiarrhythmic agent encainide have been reported after short-term intravenous and oral administration. Only prolongation of the HV interval and QRS duration have been described immediately after short-term intravenous administration of encainide in dogs and man. However, during oral therapy or more prolonged infusions, prolongation of the AH interval and atrial and ventricular effective refractory periods have also occurred. In most patients receiving encainide therapy, metabolites (O-demethyl encainide and 3-methoxy-O-demethyl encainide) accumulate during prolonged therapy to concentrations greater than those of the parent drug. We compared the electrophysiologic action of O-demethyl encainide with that of saline in anesthetized dogs to determine if this metabolite has pharmacologic activity and whether its electrophysiologic effects could account for the disparities noted between effects of intravenous and oral encainide therapy. An initial pharmacokinetic evaluation allowed design of a series of loading and maintenance infusions that produced plasma concentrations similar to those seen during encainide therapy in man (concentration after first maintenance dose, 149 +/- 27 ng/ml [+/- SE] and after second maintenance dose, 230 +/- 45 ng/ml). Significant increases in atrial effective refractory period and ventricular refractoriness, and prolongation of AH interval and HV conduction time were observed. These effects are similar to those reported after prolonged oral encainide therapy but are substantially different from those seen after short-term infusions of encainide. These findings indicate that the difference between the electrophysiologic actions of intravenous and oral encainide may be due to pharmacologic effects of at least one encainide metabolite, O-demethyl encainide.
Comparison of the electrophysiologic effects of intravenous and oral lorcainide in patients with recurrent ventricular tachycardia.
Authors: Echt D S , Mitchell L B , Kates R E , Winkle R A
Published: June 2011

The electrophysiologic effects of intravenous lorcainide (2.2 mg/kg) in 10 patients were compared with the electrophysiologic effects of oral lorcainide (mean dose 400 mg/day for 8 days) in 11 patients, all with recurrent ventricular tachycardia that could be induced with programmed stimulation. Intravenous and oral lorcainide resulted in similar prolongation of the QRS, QT, and HV intervals, but only oral lorcainide resulted in prolongation of the AH interval and atrial and ventricular effective refractory periods. After both oral and intravenous lorcainide, ventricular tachycardia could still be induced, but the arrhythmia was slower and better tolerated hemodynamically. The mean plasma lorcainide level during a maintenance intravenous infusion was 1254 +/- 662 ng/ml compared with a lorcainide level of 562 +/- 41 ng/ml and a norlorcainide level of 1212 +/- 653 ng/ml after oral dosing. No norlorcainide was detected in plasma after intravenous lorcainide. These data suggest that the short-term electrophysiologic effects of intravenous lorcainide may be different from those of short-term therapy with the oral drug. These differences should be considered during short-term studies of lorcainide.
Prognostic significance of the number of induced ventricular complexes during assessment of therapy for ventricular tachyarrhythmias.
Authors: Swerdlow C D , Winkle R A , Mason J W
Published: June 2011

We analyzed 255 long-term trials of antiarrhythmic therapy, each of which had been evaluated at electrophysiologic study, to identify the maximum number of induced ventricular complexes consistent with the long-term efficacy of antiarrhythmic therapy. All patients had spontaneous and inducible sustained ventricular tachycardia or ventricular fibrillation. The incidence of therapeutic efficacy at 1 month and throughout follow-up was similar for trials in which zero, one, two, three, four, five, six to 10, and 11 to 15 complexes were induced, but significantly lower (p less than .001) for trials in which 16 or more complexes were induced. The cumulative incidence of efficacy at 1 year was 75 +/- 5% for 0 to 5 induced complexes, 72 +/- 11% for six to 10 complexes, 83 +/- 15% for 11 to 15 complexes, 42 +/- 10% for 16 complexes to 15 sec, and 48 +/- 6% for sustained ventricular tachycardia. At 1 year, the incidence of "sudden death-free" survival was higher for patients in trials that prevented initiation of sustained ventricular tachycardia than for those in trials that permitted initiation of sustained ventricular tachycardia (91 +/- 3% vs 75 +/- 6%; p = .01). The duration of the arrhythmia induced at therapy assessment was in the range of 11 to 20 complexes for only 4% of trials. Antiarrhythmic therapy is likely to be effective if as many as 15 complexes are induced at therapy assessment. The best cutoff, between 11 and 20 complexes, is difficult to identify because of the small fraction of trials in this range. Patients in whom initiation of sustained ventricular tachycardia is not prevented are at high risk for arrhythmia recurrence and sudden death.
Late exercise test results from a prospective randomized study of bypass surgery for stable angina.
Authors: Pantely G A , Kloster F E , Morris C D
Published: June 2011

A prospective randomized study comparing coronary bypass surgery (group 1, 51 patients) to drug therapy (group 2, 49 patients) was initiated in 1981. Supine graded exercise testing (SGXT) was performed initially, at 6 months, and annually with a bicycle ergometer. The presence or absence of ischemic ST segment changes (positive or negative SGXT) and chest pain were recorded. Initially, 63% of all patients had positive SGXT. For group 2, the frequency of positive SGXT results did not change significantly at 6 months (58%) or at 5 years (52%). At 6 months the number of patients without chest pain increased in group 1 compared with group 2 (28/41 vs 13/41, respectively; p less than .002), but there was no difference in the frequency of positive SGXT results (20/41 vs 24/41, respectively; p = NS). This occurred because a majority of the group 1 patients with positive SGXT no longer had associated chest pain (group 1, 11/20, group 2, 3/24; p less than .007). This response was associated with incomplete revascularization in eight of these 11 group 1 patients and may result from "silent ischemia." At 5 years, no significant difference existed in the incidence of positive SGXT (group 1, 10/32 vs group 2, 12/23; p = NS), but group 1 patients continued to have a reduction (although not statistically significant) in the number of patients without chest pain (group 1, 19/32 vs group 2, 7/23). The incidences of death and myocardial infarction were not significantly different between groups. Fewer episodes of unstable angia occurred in group 1 (10/51 vs 19/49; p less than .05). The prognosis of group 1 patients with positive SGXT and no chest pain and incomplete revascularization was not different from that of the entire group.
Significance of systemic vascular resistance in determining the hemodynamic effects of hydralazine on large ventricular septal defects.
Authors: Nakazawa M , Takao A , Chon Y , Shimizu T , Kanaya M , Momma K
Published: June 2011

The hemodynamic effects of hydralazine were studied in 17 infants and young children with ventricular septal defects to clarify the significance of systemic vascular resistance (SVR) in determining these effects. Patients with peak pulmonary arterial pressures greater than 75% of systemic pressure were placed in group I, which was further divided into group Ia (n = 6), consisting of those with a control SVR of 20 U.m2 or higher, and group Ib (n = 8), consisting of those with a lower SVR. Group II consisted of three patients with lower pulmonary arterial pressures. Intravenous injection of hydralazine (0.3 mg/kg) reduced SVR in all but two patients. The magnitude of reduction correlated with prehydralazine (control) SVR (r = .66, p less than .01). Systemic blood flow (Qs) increased from 3.7 +/- 0.7 to 5.0 +/- 0.8 l/min/m2 (p less than .005). The mean systemic arterial pressure for all patients decreased from 69 +/- 2 to 65 +/- 2 mm Hg (p less than .01) and the mean pulmonary arterial pressure decreased from the control value by 9 +/- 4% (p less than .01) in group I and by 17 +/- 1% in group II. Pulmonary blood flow (Qp) did not change significantly in either group. The Qp/Qs ratio was reduced from 3.6 +/- 0.4 to 2.4 +/- 0.2 (p less than .02) in group Ia. In sharp contrast, however, it increased from 2.6 +/- 0.3 to 3.3 +/- 0.5 (p = .06) in group Ib. The posthydralazine Qp/Qs ratio, expressed as percent of the control value, inversely correlated with the control SVR (r = -.61, p = .02) in group I. The response was not different in the group II patients. Thus, we conclude that control SVR is important for prediction of the hemodynamic effects of afterload reduction by hydralazine in infants and young children with large ventricular septal defects, and that this drug may be beneficial in patients with high control SVRs since a high SVR brings about a decrease in the Qp/Qs ratio.
Predictive value of systolic blood pressure in young men for elevated systolic blood pressure 12 to 15 years later.
Authors: Froom P , Bar-David M , Ribak J , Van Dyk D , Kallner B , Benbassat J
Published: June 2011

Systolic blood pressure (SBP) was determined annually for 12 to 15 years in 719 men, 18 to 30 years old at entry into the study. SBP values at entry were compared with those measured in the same individuals at the end of the follow-up period. The cutoff point separating "normal" from "elevated" SBP was arbitrarily set at 140 mm Hg. The highest SBP recorded at entry was 170 mm Hg. Elevated SBP on follow-up was 2.3 times more common among subjects with elevated SBP at entry. Yet, 89.2% of the subjects with elevated SBP at entry had a normal SBP on follow-up. A normal SBP at entry did not reduce the risk of elevated SBP on follow-up.
Circadian variation of blood pressure in autonomic failure.
Authors: Mann S , Altman D G , Raftery E B , Bannister R
Published: June 2011

We have monitored ambulant intra-arterial blood pressure with the Oxford system in six subjects with autonomic failure who exhibited postural hypotension. Plotting pooled hourly mean values we have demonstrated a consistent circadian trend in blood pressure that was the inverse of the normal pattern, with the highest pressures at night and the lowest in the morning. In four subjects, confinement to bed did not substantially alter this pattern. Heart rate variability was much reduced in four of the subjects, but relatively normal in two in whom blood pressure variation was also less abnormal. There was a correlation of the nadir of the blood pressure measurements with the reported time of peak incidence of orthostatic symptoms. These findings are of importance in both the management and physiologic testing of patients with this condition.
Clinical pharmacology of propafenone.
Authors: Connolly S J , Kates R E , Lebsack C S , Harrison D C , Winkle R A
Published: June 2011

We determined the efficacy, pharmacokinetics, and plasma concentration-response relationships of propafenone, a promising new antiarrhythmic drug. Thirteen patients with frequent and complex ventricular premature beats were studied after receiving four increasing doses, during drug washout and during a randomized double-blind placebo-controlled trial, to evaluate the optimal dose in each patient. A nonlinear relationship was found between propafenone dose and steady-state mean concentration with a 10-fold increase in drug concentration as dose increased threefold from 300 to 900 mg/day. There was great intersubject variability in elimination half-life (mean 6 hr, range 2.4 to 11.8), steady-state mean concentration on 900 mg/day of propafenone (mean 1008 ng/ml, range 482 to 1812), and "therapeutic" plasma concentration (mean 588 ng/ml, range 64 to 1044). The interaction of these three parameters in individual patients determined the duration of the antiarrhythmic action of propafenone during washout (mean 11.5 hr, range 4 to 22). There was a greater than 90% reduction of ventricular premature beats in 10 subjects during dose ranging and in seven during double-blind crossover. Side effects requiring discontinuation of the drug occurred in three patients and included apparent worsening of arrhythmias in two. We conclude that propafenone effectively suppresses ventricular arrhythmias and that nonlinear drug accumulation and intersubject variability in elimination of half-life, steady-state mean plasma concentration, and therapeutic concentration indicate a need for individual therapy.
Recording of diastolic slope from the junctional area in dogs with junctional rhythm.
Authors: Hariman R J , Chen C M
Published: June 2011

Stable junctional rhythm was induced in 14 of 25 anesthetized dogs by exclusion of the sinus node and surrounding atrial tissue. In 12 of the 14 dogs diastolic slope was recorded through a unipolar lead consisting of a terminal of a plunge or catheter electrode placed in the His bundle area coupled with an indifferent superior vena caval electrode. Reversed polarity, high-gain amplification (0.1 mV/cm), and low-pass filters (0.1 to 50 Hz) were used for the unipolar recording. The diastolic slope (0.15 +/- 0.07 mV/sec) was recorded from a localized area close to the His bundle and preceded the bipolar His bundle deflection. Overdrive atrial stimulation was followed by slowing of the junctional rate and decrease in the diastolic slope. A strong negative correlation (r values from -.78 to -.95) was found between the junctional cycle lengths and the diastolic slopes after atrial pacing. Isoproterenol infusion increased the junctional rate and the diastolic slope, whereas vagal stimulation and verapamil injection decreased them. The effects of verapamil were partly reversed by CaCl2 injection. The responses of the diastolic slope to overdrive pacing, vagal stimulation, and isoproterenol suggest that the deflection is indeed due to membrane current responsible for phase 4 depolarization. The responses of the junctional rhythm and the diastolic slope to verapamil and CaCl2 suggest that AV nodal automaticity is responsible for the rhythm. Clinical application of this recording technique should help in the identification and characterization of automatic junctional rhythm.
Localization and mechanism of ventricular tachycardia by ice mapping 1 week after the onset of myocardial infarction in dogs.
Authors: Gessman L J , Agarwal J B , Endo T , Helfant R H
Published: June 2011

We developed a new technique of "ice mapping" to localize the site of termination of ventricular tachycardia in dogs 4 to 8 days after the onset of myocardial infarction. During programmed stimulation-induced ventricular tachycardia, the epicardium was mapped by moving an ice probe with a 1 cm tip over the infarct, lateral border, and normal areas. In 31 of 46 morphologically distinct sustained ventricular tachycardias, a specific area could be found that reproducibly terminated ventricular tachycardia. During ventricular tachycardia, bridging or late diastolic electrical activity was recorded from ice termination sites. In vitro microelectrode studies of 10 ice termination sites revealed slow conduction, but no spontaneous or triggered automaticity or delayed afterdepolarizations. Conduction slowed to complete block when the Tyrode perfusate was cooled from 37 degrees to 27 degrees C. We conclude that ice mapping can physiologically localize a site responsible for maintenance of ventricular tachycardia by termination of the arrhythmia, and that the presence of bridging or late diastolic electrical activity, slow conduction with cooling-induced block, and absence of spontaneous or triggered automaticity or delayed afterdepolarizations suggest that local cooling terminates ventricular tachycardia by slowing or blocking conduction in a reentrant loop.
Myocardial salvage by intravenous nitroglycerin in conscious dogs: loss of beneficial effect with marked nitroglycerin-induced hypotension.
Authors: Jugdutt B I
Published: June 2011

We studied the effect of nitroglycerin-induced decreases in mean arterial pressure (MAP) on myocardial salvage. Two hours after occlusion of the left anterior descending coronary artery, 65 conscious dogs were randomly allocated to receive 4 hr intravenous infusions of saline (group 1, 19 dogs), or nitroglycerin in doses to decrease MAP by 10% (group 2, 18 dogs), 25% (group 3, 14 dogs), and 50% (group 4, 14 dogs), respectively. At 7 days, 41 dogs were killed for measurement of infarct size; 24 dogs, given 7 to 10 micron radioactive microspheres for flow calculations, were killed 6 hr after occlusion. Boundaries of the occluded bed were defined by postmortem coronary arteriography. Infarct and occluded bed masses were measured by planimetry of weighed transverse sections of the left ventricle. Compared with saline infusions in group 1, nitroglycerin infusions produced sustained reductions (p less than .001) in mean left atrial pressure and MAP in all dogs, but heart rate was unchanged. The decreases in MAP achieved in groups 2, 3, and 4 were 10% (range, 5% to 19%), 23%, and 39%, respectively, with average levels of 96 (range, 83 to 113), 83, and 64 mm Hg, respectively. Despite similar masses of the occluded bed and left ventricle among the four groups, infarct size was significantly smaller (p less than .025) in group 2 compared with groups 1, 3, or 4, expressed both as percent of the left ventricle (6% vs 14% vs 13% vs 15%) and as percent of the occluded bed (13% vs 37% vs 34% vs 44%). Myocardial salvage (expressed as percent of the occluded bed) with nitroglycerin correlated inversely with the percent of decrease in MAP (r = -.77, p less than .001). Collateral blood flow increased (p less than .005) throughout the occluded bed in group 2 compared with group 1 but was unchanged in groups 3 and 4. In contrast, coronary vascular resistance decreased (p less than .025) in all nitroglycerin groups. These results suggest that perfusion pressure is an important determinant of myocardial salvage during nitroglycerin therapy. An increase in the dose of nitroglycerin to decrease MAP by more than 10%, and to levels below 96 mm Hg, might offset its potential for myocardial salvage in the conscious dog.
Beta-adrenergic receptor and cyclic AMP alterations in the canine ventricular septum during long-term norepinephrine infusion: implications for hypertrophic cardiomyopathy.
Authors: Raum W J , Laks M M , Garner D , Swerdloff R S
Published: June 2011

Norepinephrine infusion in dogs has been shown to cause ventricular septal hypertrophy that mimics the syndrome of hypertrophic cardiomyopathy in humans. To characterize the mechanisms involved in septal hypertrophy, the adrenergic system of the right and left ventricles and the septum were analyzed before and after norepinephrine infusion. In the normal unperturbed state, the septum was found to be more sensitive to beta-adrenergic stimulation than either the right or left ventricles. That is, more cyclic AMP could be generated with a smaller dose of beta-agonist (isoproterenol) in septal tissue homogenate than in homogenates of the right or left ventricles. With infusions of norepinephrine (1.4 micrograms/min) to subhypertensive levels over 3 months, beta-receptor number increased twofold to threefold in the ventricles and septum. Adenylate cyclase activity also increased in the ventricles, but not in the septum. The sensitivity of adenylate cyclase to beta-agonist stimulation increased in the septum but remained unchanged in the right and left ventricles. We conclude that the alterations in the myocardial adrenergic system occur in response to the norepinephrine infusion and are not a consequence of hypertrophy. We formulated a hypothesis suggesting that depleted tissue stores of cyclic AMP and/or adenosine triphosphate may be one of the mechanisms involved in the development of hypertrophic cardiomyopathy.
Value of partial ejection fraction, volume increment, and regional wall motion in identifying patients with clinically significant coronary artery disease.
Authors: Sheehan F H , Dodge H T , Bolson E L , Woo H W , Caputo G R , Stewart D K
Published: June 2011

Recent studies suggest that the partial ejection fraction (EF) in early systole is a more sensitive index of left ventricular (LV) dysfunction than the holosystolic EF. We examined LV volume, partial EF, and volume increment at each of 12 time points in systole to determine which parameter best distinguishes normal subjects from patients with coronary artery disease (CAD). Contrast ventriculograms, obtained either in the right anterior oblique projection (60 frames/sec) or in the biplane projection (30 frames/sec), of 58 normal subjects and 68 patients with CAD were studied. The endocardial contour in each frame of a sinus beat was traced to derive a volume curve. At each twelfth of systole, LV volume was extrapolated from the curve and the partial EF was calculated. The increment in volume between successive time points was also calculated. Both partial EF and LV volume in patients with CAD became progressively more abnormal with time; peak abnormality occurred at end-systole. In a subgroup of patients with CAD who had normal holosystolic EF, both partial EF and volume were normal throughout systole. The increment in volume with each twelfth of systole in patients with CAD deviated less than 1 SD from normal throughout systole. Thus, maximum abnormality in partial EF and volume occurs at end-systole. Of the parameters of global LV function tested, holosystolic EF best distinguishes patients with CAD from normal subjects. However, regional wall motion measured in the area of interest is more sensitive to localized abnormality, the severity of which may be overestimated or underestimated by the EF due to hyperkinesis or hypokinesis in other regions of the left ventricle.
Quantitative x-ray microanalysis of the elemental composition of individual myocytes in hypoxic rabbit myocardium.
Authors: Buja L M , Burton K P , Hagler H K , Willerson J T
Published: June 2011

The purpose of this study was to use energy dispersive x-ray microanalysis to test the following hypotheses: (1) that individual myocytes may exhibit important variation in the severity of alterations in intracellular ionic homeostasis in response to hypoxia and (2) that hypoxic myocytes may accumulate certain elements in quantities sufficient to impair organellar function and structure. A rabbit interventricular septal preparation with attached small right ventricular papillary muscles was used to obtain control oxygenated myocardium (six papillary muscles) and myocardium rendered hypoxic for 1 to 1 1/2 hr (n = 8). Myocardium not perfused in vitro was also obtained (n = 4). Microanalysis was performed on freeze-dried thin sections of unfixed papillary muscles. Elemental concentrations were determined by suitable cryostandards of elements of interest. Sarcoplasm and mitochondria of most hypoxic myocytes exhibited significant alterations of diffusible elements, including increases in sodium and chloride and decreases in potassium, phosphorus, and magnesium, without major change in calcium. The most severely altered myocytes showed evidence of calcium overloading manifested by markedly increased levels of mitochondrial calcium and phosphorus associated with formation of electron-dense mitochondrial inclusions. Levels of mitochondrial calcium and phosphorus exceeded those previously found to markedly impair the function and structure of isolated mitochondria. Thus x-ray microanalysis of unfixed cryosections provides direct measurements of subcellular alterations in elemental composition of individual myocytes in injured myocardium and demonstrates that both calcium and phosphorus accumulate in mitochondria of severely injured myocytes in concentrations sufficient to exert deleterious effects on these organelles.
Quantitative two-dimensional echocardiographic analysis of motion and thickening of the interventricular septum after cardiac surgery.
Authors: Force T , Bloomfield P , O'Boyle J E , Pietro D A , Dunlap R W , Khuri S F , Parisi A F
Published: June 2011

Septal and lateral wall motion and septal thickening were evaluated with quantitative two-dimensional echocardiography in 20 patients who underwent cardiac surgery without complications. Postoperative mean ejection fraction (48 +/- 10%) measured by radionuclide ventriculography was unchanged from the preoperative value (45 +/- 8%). Mean postoperative systolic thickening of the septum (33 +/- 15%) was also unchanged from the preoperative value (26 +/- 10%). However, septal endocardial motion as measured by an external frame-of-reference (fixed-axis) system fell from a 22 +/- 10% mean percent shortening (MPS) of septal radii to a postoperative value of -8 +/- 15% (p less than .001). Fixed-axis analysis also led to an increase in MPS of lateral radii: preoperative 16 +/- 5%; postoperative 28 +/- 9% (p less than .001). With an internal frame-of-reference (floating-axis) system, which compensates for the effects of translation and rotation on wall motion, postoperative MPS of septal radii (22 +/- 10%) was unchanged from preoperative MPS (25 +/- 8%; p = NS). Similarly, MPS of lateral wall radii was unchanged (preoperative, 15 +/- 5%; postoperative, 12 +/- 5%; p = NS). Thus systolic translation of the ventricle accounts for abnormal postoperative septal motion seen in a fixed-axis system and can be corrected by a floating-axis system. These data have important implications for the noninvasive evaluation of regional wall motion after cardiac surgery. Systems using a fixed external frame of reference such as radionuclide ventriculography are prone to systematic error. A combination of systolic thickening analysis by two-dimensional echocardiography and analysis of endocardial motion by the floating-axis system is a more appropriate method for evaluating the effects of cardiac surgery on regional left ventricular function.
Differential electrocardiographic effects of myocardial ischemia induced by atrial pacing in dogs with various locations of coronary stenosis.
Authors: Mirvis D M
Published: June 2011

The spatial distribution of abnormal repolarization potentials caused by regional myocardial ischemia was determined in 45 dogs. Ameroid constrictors were placed around the left circumflex artery in 10, the left anterior descending artery in 10, and the right coronary artery in 10. Ten dogs without constrictors served as controls. Electrocardiographic events were determined from body surface isopotential distributions, which were computed from potentials sensed by 84 torso electrodes. In control dogs, pacing to heart rates of 230 to 250 beats/min increased the intensity of positive and negative surface extrema during the ST segment without altering their spatial features. Two weeks after placement of the ameroid constrictors, tachycardia induced abnormal negative potentials during the ST segment. Localization of these ischemic forces varied with the placement of the constrictor in a manner consistent with the affected perfusion territories. However, much of the torso surface was involved by all lesions, and only small zones of ST segment depression unique to specific lesions could be identified. In five additional dogs a constrictor was placed on the right coronary artery 3 months after implantation of a device on the circumflex vessel. ST segment patterns during pacing in dogs with two lesions were consistent with the sum of the two individual lesions. Thus, the regional nature of myocardial ischemia is detectable in the body surface isopotential distributions, but the degree of spatial overlap may limit the value of such techniques in extending the usefulness of clinical exercise-stress electrocardiography.
Replacement of aortic valve combined with myocardial revascularization: determinants of early and late risk for 500 patients, 1967-1981.
Authors: Lytle B W , Cosgrove D M , Loop F D , Taylor P C , Gill C C , Golding L A , Goormastic M , Groves L K
Published: June 2011

Five hundred consecutive patients underwent aortic valve replacement and coronary revascularization in the years from 1967 to 1981, with 29 (5.9%) in-hospital deaths. Current operative mortality (1978-1981) is 3.4%. Univariate and multivariate analyses were used to identify determinants of early and late risk. Female sex, aortic insufficiency, and advanced age increased in-hospital mortality, whereas use of cardioplegia decreased it. At follow-up of 471 patients who survived hospitalization for 1 to 135 months (mean 41) after surgery, 96 late deaths were documented. Survival rates were 87%, 80%, and 55%, and event-free survival rates were 80%, 65%, and 39% at 2, 5, and 10 years after surgery, respectively. The late survival rate was unfavorably influenced by the presence of moderately or severely impaired left ventricular function and double-vessel coronary disease; the rate was enhanced for patients in age group from 50 to 59 years old and was not influenced by the method of myocardial protection. The event-free survival rate decreased with the presence of moderately or severely impaired left ventricular function and was enhanced for patients with New York Heart Association class I or II symptoms before surgery. Patients with bioprostheses who did not receive anticoagulants had higher survival and event-free survival rates than did either patients with bioprostheses who received anticoagulants or patients with mechanical valves, whether they received anticoagulants or not.
Potentiation of the cardiovascular effects of nitroglycerin by N-acetylcysteine.
Authors: Horowitz J D , Antman E M , Lorell B H , Barry W H , Smith T W
Published: June 2011

The biochemical basis of the mechanism of vasodilatation by nitroglycerin (NTG) has not been previously investigated in man. However, evidence from in vitro studies suggests that NTG induces activation of guanylate cyclase via a series of enzymatic reactions that are modulated by the availability of sulfhydryl groups. Cysteine appears to be particularly effective in potentiating guanylate cyclase activation by NTG. To determine whether hemodynamic responsiveness to NTG in man might be modulated by sulfhydryl availability, concentration-response curves for effects of intravenously infused NTG on mean arterial pressure (MAP) and mean pulmonary capillary wedge pressure (PCW) were obtained in 10 patients undergoing cardiac catheterization for investigation of chest pain. NTG infusion was repeated 10 min after the intravenous infusion of 100 mg/kg of the cysteine source N-acetylcysteine (NAC). NAC induced no significant hemodynamic effect, but after NAC infusion there was a significant reduction both in the NTG infusion rate associated with a 10% fall from control values in MAP (25.8 +/- 8.3 to 9.3 +/- 2.7 micrograms/min; p less than .01) and in the infusion rate inducing a 30% reduction in PCW (13.6 +/- 4.6 to 4.2 +/- 1.6 micrograms/min; p less than .02). In a control group of five patients who received no NAC, there was no significant change in responsiveness to NTG between infusions. It is concluded that NAC potentiates the vasodilator effects of NTG in man. This suggests that sulfhydryl availability and/or redox state may be determinants of in vivo responsiveness to NTG.
Comparative effects of propranolol and verapamil alone and in combination on left ventricular function and volumes in patients with chronic exertional angina: a double-blind, placebo-controlled, randomized, crossover study with radionuclide ventriculography.
Authors: Johnston D L , Gebhardt V A , Donald A , Kostuk W J
Published: June 2011

With the use of equilibrium radionuclide ventriculography the effects on left ventricular (LV) function of 160 mg oral propranolol daily and 360 mg verapamil daily alone and in combination were compared in 18 patients with chronic exertional angina. A randomized, double-blind, placebo-controlled, crossover protocol was used. The reduction in exercise rate-pressure product induced by the combination (118 +/- 28 mm Hg/min) was significantly greater (p less than .05) than that by propranolol (135 +/- 27 mm Hg/min) or verapamil alone (163 +/- 28 mm Hg/min). In patients at rest, neither single nor combined therapy altered global or regional left ventricular ejection fractions (EFs). Verapamil, but not propranolol, increased (p less than .05) cardiac volumes of resting subjects; used in combination, no further increase in LV volume occurred. With placebo, exercise global EF did not decrease from the level at rest and therefore no drug effect could be demonstrated for this parameter of LV function. By an evaluation of normalized regional EF measurements the combination was shown to reduce exercise-induced hypokinesis (placebo 52 +/- 20%, combination 61 +/- 23%; p less than .01). No significant improvement was noted with propranolol or verapamil alone; only the combination prevented a significant increase in end-systolic and end-diastolic volumes during exercise. Thus, propranolol and verapamil, used alone in moderate doses, exert no beneficial effect on exercise LV function as measured by EF and volume changes, and resting function deteriorates slightly with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of pericardium on the end-systolic pressure-segment length relationship in canine left ventricle in acute volume overload.
Authors: Kanazawa M , Shirato K , Ishikawa K , Nakajima T , Haneda T , Takishima T
Published: June 2011

The effect of the pericardium on the end-systolic pressure-segment length relationship in the left ventricle was examined with an ultrasonic miniature gauge in open-chest dogs. In 12 dogs, blood was infused until left ventricular (LV) end-diastolic pressure reached about 20 mm Hg, and then the pericardium was opened widely. In the other 12 dogs a pericardiectomy was performed without blood infusion. Stroke volume was measured in six dogs in the former group and in seven dogs in the latter group. After blood infusion, LV systolic, end-systolic, and end-diastolic pressures increased from 120 +/- 14 to 162 +/- 16 mm Hg (mean +/- SD), from 106 +/- 13 to 146 +/- 17 mm Hg, and from 8 +/- 2 to 19 +/- 2 mm Hg, respectively (all p less than .01). End-systolic and end-diastolic segment lengths increased from 8.9 +/- 2.1 to 10.6 +/- 2.2 mm and from 11.6 +/- 2.5 to 14.9 +/- 2.7 mm, respectively (both p less than .01). After pericardiectomy, the segments were further lengthened by 8.9 +/- 4.4% and by 10.0 +/- 6.2%, respectively (both p less than .01). Heart rate, LV systolic and end-systolic pressures, and peak positive dp/dt did not change, although end-diastolic pressure fell from 19 +/- 2 to 18 +/- 2 mm Hg (p less than .01). Stroke volume rose from 13.1 +/- 3.7 to 23.9 +/- 5.0 ml due to volume loading and further increased by 26.7 +/- 9.0% after pericardiectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of substituted sydnonimines on coronary smooth muscle relaxation and cyclic guanosine monophosphate levels.
Authors: Rinaldi G , Cingolani H
Published: June 2011

In vitro experiments on precontracted canine coronary arteries were performed to study the direct relaxant effects of molsidomine (MOLS) and its active metabolite, SIN-1, and to determine if there is a relationship between effect and cGMP level elevations. The effects of MOLS and SIN-1 were compared with those of a classic vasodilator, nitroglycerin (NTG). At equimolar doses (10(-6)M) SIN-1 exerted greater relaxant effect than NTG (80 +/- 2% and 60 +/- 5%, respectively) in spite of the fact that it produced less of an increase in cyclic guanosine monophosphate (cGMP) levels. cGMP levels fell rapidly after they peaked, but relaxation was maintained. cGMP elevation preceded the induction of relaxation by NTG but not that induced by SIN-1. Relaxation occurred faster after NTG than after SIN-1. Since SIN-1 has a greater relaxant effect than NTG in spite of the fact that SIN-1 induces less of an increase in cGMP levels and the fact that the peak elevation does not precede the onset of relaxation, the causal nexus between GMP level elevation and relaxation effect after sydnonimines should be challenged.
Dipyridamole dilates large coronary arteries in conscious dogs.
Authors: Hintze T H , Vatner S F
Published: June 2011

The effects of 0.25 mg/kg dipyridamole on left ventricular (LV) pressures, LV dP/dt, heart rate, aortic pressures, left circumflex coronary blood flow, and left circumflex coronary arterial diameters and on calculations of late diastolic coronary resistance and large coronary cross-sectional area were studied in 15 conscious dogs. Injection of dipyridamole, a drug that has a mechanism of action dependent on myocardial adenosine production, caused sustained increases in mean coronary blood flow (244 +/- 28%), large coronary arterial cross-sectional area (28 +/- 3.2%), heart rate (32 +/- 3.6%), and LV dP/dt (23 +/- 3.0%) and reductions in late diastolic coronary resistance (73 +/- 2.4%) and mean arterial pressure (14 +/- 1.9%). Neither beta-adrenergic-receptor blockade alone nor in conjunction with constant heart rate affected the dilation of large coronary arteries to dipyridamole significantly. Ganglionic blockade with hexamethonium also had little effect on the response of large and small coronary vessels to dipyridamole. Surprisingly neither beta-adrenergic-receptor nor ganglionic blockade abolished the rise in LV dP/dt observed after dipyridamole. Aminophylline, however, effectively eliminated the dilation of large coronary arteries and resistance coronary vessels in response to dipyridamole. In summary, as long as dipyridamole does not induce severe sustained hypotension it exerts potent effects on both coronary arterial resistance and large coronary arteries in the conscious dog. The coronary dilation is independent of reflex adrenergic activation, but appears dependent on myocardial adenosine production.