bluuebunny/crossref_metadata_2025 huggingface dataset:
AH23848: a thromboxane receptor-blocking drug that can clarify the pathophysiologic role of thromboxane A2.
Authors: Brittain R T , Boutal L , Carter M C , Coleman R A , Collington E W , Geisow H P , Hallett P , Hornby E J , Humphrey P P , Jack D
Published: June 2011

Despite numerous suggestions in the literature that thromboxane A2 is involved in a variety of occlusive vascular diseases, no definitive evidence is available. Arguments have been presented to support the view that such evidence can only come from clinical studies with a highly specific thromboxane receptor-blocking drug. We have now identified such a drug, AH23848, in our laboratories. Preliminary experiments with AH23848, ([1 alpha (Z), 2 beta,5 alpha]-(+/-)-7-[5-[[(1,1'-biphenyl)-4-yl]methoxy]-2-(4-morpholin yl)-3-oxocyclopentyl]-4-heptenoic acid), show that it is a potent, specific thromboxane receptor-blocking drug that is orally active and has a long duration of action. It should be a valuable tool in elucidating any physiologic or pathologic role of thromboxane A2.
The hypotensive effect of intravenous streptokinase in patients with acute myocardial infarction.
Authors: Lew A S , Laramee P , Cercek B , Shah P K , Ganz W
Published: June 2011

We studied the hypotensive effect of a rapid intravenous infusion of high-dose streptokinase in 98 patients with an acute myocardial infarction. The systolic blood pressure fell from 132 +/- 20 (range 90 to 174) to 97 +/- 21 mm Hg (range 58 to 152) at 15 +/- 8 min (range 4 to 40) after the commencement of the streptokinase infusion (p less than .001). A fall in diastolic blood pressure from 80 +/- 16 (range 51 to 105) to 61 +/- 15 mm Hg (range 32 to 92) accompanied the fall in systolic pressure (p less than .001). The fall in blood pressure was associated with an increase in heart rate (73 +/- 14 to 78 +/- 17 beats/min, p less than .001), preceded the appearance of clinical signs of reperfusion by 37 +/- 38 min and was similar in magnitude and timing in patients with anterior and inferior infarction. There were direct relationships between the rate of infusion of streptokinase and both the magnitude (r = .49, p less than .001) and the rate of fall of systolic blood pressure (r = .67, p less than .001) as well as both the magnitude and rate of fall of diastolic blood pressure. In most patients, the fall in blood pressure was transient (9 +/- 6 min, range = 2 to 30) and easily managed by slowing or stopping the infusion, placing the patient in the Trendelenburg position, or by administering an infusion of low-dose norepinephrine or dopamine. However, in four patients with severe left ventricular dysfunction, severe hypotension persisted for more than 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Unexpected effects of treating hypertension in men with electrocardiographic abnormalities: a critical analysis.
Authors: Kuller L H , Hulley S B , Cohen J D , Neaton J
Published: June 2011

The relationship between diuretic therapy and possible increased risk of coronary heart disease (CHD), especially sudden death, is controversial. The initial report from the Multiple Risk Factor Intervention Trial (MRFIT) raised the possibility that the increased CHD mortality observed in a subset of special intervention men with hypertension and certain electrocardiographic abnormalities on their baseline examination might be an unexpected adverse effect of diuretic therapy. Subsequent reports from the MRFIT have revealed a stronger association of CHD mortality to hydrochlorothiazide than to chlorthalidone. There was no consistent relationship of CHD mortality to the dose of either drug, to the most recent serum potassium level, or to the presence of ventricular premature beats. Unfavorable trends of the same magnitude were also seen among similar white men in the Hypertension Detection and Follow-up Program and in the Oslo hypertension trial, although the sample sizes in these two studies were too small to yield clearcut conclusions. Clinical studies have shown an increased risk of CHD death among hypertensive men with left ventricular hypertrophy. Such men are also noted to have a higher frequency of ventricular premature beats, even in the absence of diuretic therapy. Other studies have shown that diuretic-induced hypokalemia is accentuated in the presence of epinephrine and that low potassium levels decrease the threshold for ventricular fibrillation. Thus, although the evidence is still incomplete, it is possible that the excess CHD mortality among MRFIT special intervention men with electrocardiographic abnormalities may have been caused by a combination of increased left ventricular mass in the presence of coronary atherosclerosis, and hypokalemia caused by good compliance with diuretic therapy and accentuated by stress-induced increases in circulating catecholamines. Given the very large population of patients receiving diuretic therapy, further evaluation of this possibility is important.
Potentiation of nitroglycerin-induced coronary dilatation by N-acetylcysteine.
Authors: Winniford M D , Kennedy P L , Wells P J , Hillis L D
Published: June 2011

Previous studies have suggested that (1) nitroglycerin causes vasodilatation by interacting with sulfhydryl groups in vascular smooth muscle, thereby activating guanylate cyclase and increasing the intracellular concentration of cyclic GMP, and (2) N-acetylcysteine, a source of sulfhydryl groups, potentiates the peripheral vasodilatory effect of nitroglycerin. This study was performed to explore the influence of N-acetylcysteine on nitroglycerin-induced coronary dilatation. In 18 patients (13 men and five women, 30 to 76 years old), coronary sinus blood flow (by thermodilution) was measured before and during intracoronary administration of nitroglycerin, 25 micrograms, both before and 5 min after a 15 min intravenous infusion of (1) 5% dextrose in water (n = 8, control) or (2) 100 mg/kg N-acetylcysteine (n = 10). Nitroglycerin caused no change in heart rate or systemic arterial pressure. In the control patients, coronary sinus blood flow behaved similarly during the two injections: it was 134 +/- 36 ml/min (mean +/- SD) before and 183 +/- 50 ml/min during injection No. 1 (average increase, 49 +/- 25 ml/min; average percent increase, 38 +/- 21%); and it was 131 +/- 34 ml/min before and 178 +/- 45 ml/min during injection No. 2 (average increase, 47 +/- 23 ml/min; average percent increase, 37 +/- 20%) (NS compared with injection 1). In the patients who received N-acetylcysteine, coronary sinus blood flow was 149 +/- 48 ml/min before and 191 +/- 54 ml/min during injection 1 (average increase, 42 +/- 15 ml/min; average percent increase, 30 +/- 12%) (NS compared with eight control values).(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of changes in physical activity on major cardiovascular risk factors, hemodynamics, sympathetic function, and glucose utilization in man: a controlled study of four levels of activity.
Authors: Jennings G , Nelson L , Nestel P , Esler M , Korner P , Burton D , Bazelmans J
Published: June 2011

The effects of four levels of activity on heart rate, blood pressure, cardiac index, total peripheral resistance index (TPRI), norepinephrine (NE) spillover rate, insulin sensitivity, and levels of lipids and some hormones were studied in 12 normal subjects. The randomized periods were (1) 4 weeks of below-sedentary activity, (2) 4 weeks of sedentary activity, (3) 4 weeks of 40 min of bicycling three times per week, and (4) 4 weeks of similar bicycling seven times per week. Exercise three times per week reduced resting blood pressure by 10/7 mm Hg (p less than .01) and it was reduced by 12/7 mm Hg after exercise seven times per week (both p less than .01). This was associated with reduction in TPRI, an increase in cardiac index, and cardiac slowing. At the highest level of activity, NE spillover rate, an index of sympathetic activity, fell to 35% of the sedentary value (p less than .001) in eight of 10 subjects. In two other subjects NE spillover rate rose, although blood pressure and TPRI were reduced. Metabolic changes included lowering of total cholesterol, but high-density lipoprotein level was unchanged. Insulin sensitivity rose by 27% after exercise three times per week, but declined to sedentary levels with seven times per week exercise. Maximum oxygen uptake increased linearly with activity. Exercise performed three times per week lowers blood pressure and should reduce cardiovascular risk. The same exercise seven times per week enhances physical performance with little further reduction in cardiovascular risk factors. Exercise is potentially a major nonpharmacologic method of lowering blood pressure.
Relationship of contractile state to ejection performance in patients with chronic aortic valve disease.
Authors: Wisenbaugh T , Booth D , DeMaria A , Nissen S , Waters J
Published: June 2011

To assess the relative contributions of afterload mismatch and impaired contractility to pump dysfunction in patients with chronic aortic valve disease, simultaneous left ventricular cineangiography and micromanometry were performed in 56 patients: 21 with severe aortic stenosis, 16 with severe aortic regurgitation, and 19 normal control subjects. Left ventricular mass was increased in patients with aortic stenosis and aortic regurgitation (172 +/- 52 and 224 +/- 63 g/m2, respectively, vs 89 +/- 16 for control subjects; p less than .05) as were end-diastolic volume (101 +/- 39 and 167 +/- 44 vs 77 +/- 16 ml/m2; p less than .05) and end-systolic volume (50 +/- 40 and 84 +/- 43 vs 24 +/- 7 ml/m2; p less than .05). Although ejection fraction was depressed in both abnormal groups (0.56 +/- 0.18 for patients with aortic stenosis and 0.53 +/- 0.13 for those with aortic regurgitation vs 0.69 +/- 0.05 for control subjects; p less than .05), the decrease in ejection fraction was disproportionate to the mild degree of afterload mismatch (end ejection stress 129 +/- 17 in patients with aortic stenosis and 154 +/- 58 in those with aortic regurgitation vs 117 +/- 46 kdyn/cm2 in control subjects; p = NS) with 10 of 21 patients with aortic stenosis and 12 of 16 patients with aortic regurgitation falling below the 95% prediction limit of the linear inverse relationship between ejection fraction and end-systolic stress for controls (EF = 0.78 - 0.00074 X ESS).(ABSTRACT TRUNCATED AT 250 WORDS)
Blood flow pattern of the interatrial communication in patients with complete transposition of the great arteries: a pulsed Doppler echocardiographic study.
Authors: Satomi G , Nakazawa M , Takao A , Mori K , Touyama K , Konishi T , Tomimatsu H , Nakamura K
Published: June 2011

We analyzed blood flow pattern in the interatrial communication in 24 patients with complete transposition of the great arteries (TGA). Eight had TGA with atrial shunt (group 1), nine had TGA with patent ductus arteriosus or ventricular septal defect (group 2), and seven had pulmonary arterial banding and Blalock-Taussig shunt (group 3). The flow pattern was determined at the site of atrial septal defect by Doppler echo beam directed as perpendicular to the septum as possible. The flow pattern was composed of a left-to-right (L-R) flow and right-to-left (R-L) flow. The turning point (T1) from the R-L to L-R flow occurred immediately after the initiation of the QRS on the electrocardiogram and was common in all groups. The other turning point (T2) from L-R to R-L occurred after the second heart sound (S2). The S2-T2 interval decreased on inspiration, indicating prolongation of the period of R-L flow. The minimum S2-T2 interval ranged from 20 to 70 (mean +/- SD 50 +/- 18) msec in group 1, from 70 to 130 (114 +/- 25) msec in group 2, and from 50 to 138 (75 +/- 29) msec in group 3. The maximum S2-T2 interval ranged from 48 to 110 (88 +/- 21) msec in group 1, from 140 to 235 (175 +/- 36) msec in group 2, and from 80 to 170 (111 +/- 30) msec in group 3.(ABSTRACT TRUNCATED AT 250 WORDS)
Therapeutic opportunities in vasoocclusive disease.
Authors: Ritter J M , Dollery C T
Published: June 2011

There is evidence that aspirin is partially effective in the prophylaxis of various vasoocclusive disorders. This article reviews pharmacologic opportunities for improvement over and above the therapeutic effect of aspirin. It is concluded that several rational possibilities merit consideration, in particular, the use of combinations of drugs that affect the thrombotic process at different points. Such strategies will ultimately require validation by clinical trial.
Alteration of human right bundle branch refractoriness by changes in duration of the atrial drive train.
Authors: Miles W M , Prystowsky E N
Published: June 2011

We studied the effect of drive train duration on human right bundle branch refractoriness. Seven patients with a QRS duration of 0.10 sec or less and no preexcitation had functional right bundle branch block induced reproducibly with premature atrial stimulation. Refractoriness of the right bundle branch was defined as the longest H1H2 interval resulting in right bundle branch block and was determined in each patient at a constant pacing cycle length but at five to seven different atrial drive train durations varying from four to 99 complexes. In all seven patients, right bundle branch refractoriness decreased with increasing drive train duration (mean 15 msec). One-third of this decrease (5.0 msec) occurred between drive train durations of four and eight complexes, and close to two-thirds (9.3 msec) occurred between drive train durations of eight and 64 complexes. Very little further decrease (0.7 msec) occurred between 64 and 99 complexes. We conclude that right bundle branch refractoriness shortens progressively as the preceding drive train duration increases. This phenomenon may in part explain the disappearance of functional right bundle branch block during supraventricular tachycardia after a variable number of complexes without a change in cycle length of tachycardia.
Quantitative analysis of segmental wall motion during maximal upright dynamic exercise: variability in normal adults.
Authors: Ginzton L E , Conant R , Brizendine M , Thigpen T , Laks M M
Published: June 2011

Twenty-five healthy adults underwent subcostal-view, four-chamber two-dimensional echocardiographic examination while upright at rest and at the peak of maximal bicycle exercise. The purpose of the study was to determine whether the variability in regional left ventricular endocardial motion, previously demonstrated to be present at rest, persisted at peak exercise. The rest and exercise end-diastolic and end-systolic endocardial contours were visually identified, digitized, and divided into 32 radial segments after realignment by the computer. At rest there was similar percent segmental area reduction for the septum (segments 1 to 12) (54 +/- 4%, mean +/- 1 SD), apex (segments 13 to 20) (67 +/- 3%), and lateral wall (segments 21 to 32) (67 +/- 8%). At peak exercise the percent area reduction increased significantly: septum 84 +/- 5%, apex 88 +/- 2%, lateral wall 83 +/- 6% (p less than .001 compared with rest for all areas). However, there was considerable variability in percent area reduction between different radial segments in the same individual. At rest the difference between minimal and maximal percent area reduction within the same individual was 49 +/- 17 percentage units (range 21 to 83) and that at peak exercise was 32 +/- 17 percentage units (range 0 to 66). It is concluded that, because the range of standard deviation of normal endocardial motion and the degree of variability between radial segments in the same healthy individual are significant, qualitatively determined "hypokinesis," as commonly assessed clinically, may be a normal event. However, segmental akinesis or dyskinesis, which occurred rarely at rest and never at peak exercise, must be considered abnormal events.
Reduction of indium-111 platelet deposition on Dacron vascular grafts in humans by aspirin plus dipyridamole.
Authors: Stratton J R , Ritchie J L
Published: June 2011

Aspirin plus dipyridamole reduces platelet accumulation on short-term Dacron vascular grafts in man. To determine whether drug inhibition of platelet deposition is sustained on older grafts, we studied 18 men aged 41 to 87 years who had Dacron aortic bifurcation grafts in place a mean of 43.4 months (range 9.8 to 121.0) before and during short-term therapy with aspirin (325 mg tid) plus dipyridamole (75 mg tid). During both the baseline and drug studies, indium-111 (111In) platelet deposition was quantitated by two techniques, standard planar imaging performed at 24, 48, and 72 hr after injection of platelets and single photon emission computed tomographic imaging performed at 24 and 72 hr after injection. All analyses were performed in a blinded fashion. On both the planar and tomographic images, platelet accumulation on the graft was quantitated by a graft/blood ratio that compared activity in the graft to simultaneously collected whole blood 111In platelet activity. Aspirin plus dipyridamole reduced the tomographic graft/blood ratio at 24 hr (20.6 +/- 3.5 vs 17.3 +/- 2.5) (+/-SEM) and at 72 hr (29.0 +/- 4.8 vs 25.0 +/- 4.1) after injection of platelets (p = .02). Dacron vascular grafts. Similarly, the planar graft/blood ratio was reduced at 24 hr (2.7 +/- 0.5 vs 2.4 +/- 0.5), 48 hr (3.7 +/- 0.9 vs 3.1 +/- 0.7), and 72 hr (4.0 +/- 0.9 vs 3.6 +/- 0.8) (p = .04). We conclude that aspirin (325 mg tid) plus dipyridamole (75 mg tid) reduces platelet accumulation on long-term Dacron vascular grafts.
Effect of the addition of propranolol to therapy with nifedipine for unstable angina pectoris: a randomized, double-blind, placebo-controlled trial.
Authors: Gottlieb S O , Weisfeldt M L , Ouyang P , Achuff S C , Baughman K L , Traill T A , Brinker J A , Shapiro E P , Chandra N C , Mellits E D
Published: June 2011

The value of the addition of beta-blockers to coronary vasodilator therapy in the treatment of patients with unstable angina at rest is controversial. We conducted a double-blind, randomized, placebo-controlled 4 week trial of propranolol in 81 patients with unstable angina, 39 of whom were assigned to placebo and 42 of whom received propranolol in a dose of at least 160 mg daily. All patients were also treated with coronary vasodilators, including 80 mg nifedipine daily and long-acting nitrates. The incidences of cardiac death, myocardial infarction, and requirement for bypass surgery or coronary angioplasty did not differ between the two groups (propranolol = 16; placebo = 18). The propranolol group had a lower cumulative probability of experiencing recurrent resting angina than the placebo group (p = .013), and over the first 4 days of the trial the mean number of clinical episodes of angina (propranolol 0.9 +/- 0.2, placebo 1.8 +/- 0.3, p = .036), duration of angina (propranolol 15.1 +/- 4.3 min, placebo 38.1 +/- 8.4, p = .014), and nitroglycerin requirement (propranolol 1.1 +/- 0.3 tablets, placebo 3.5 +/- 0.8, p = .003) were also fewer. Continuous electrocardiographic recording for ischemic ST segment changes revealed fewer daily ischemic episodes in the propranolol group (2.0 +/- 0.5) than in the placebo group (3.8 +/- 0.7, p = .03), and a shorter duration of ischemia (propranolol 43 +/- 10 min, placebo 104 +/- 28 min, p = .039). Thus propranolol, in patients with unstable angina, in the presence of nitrates and nifedipine is not detrimental and reduces the frequency and duration of symptomatic and silent ischemic episodes.
Enhanced peripheral vasoconstrictor response and increased thromboxane A2 synthesis after the cold pressor test in patients with angina at rest.
Authors: Neri Serneri G G , Gensini G F , Masotti G , Abbate R , Poggesi L , Laureano R , Prisco D , Rogasi P G , Castellani S
Published: June 2011

Peripheral vascular resistance (PVR) and thromboxane A2(TxA2) synthesis after the cold pressor test were investigated in different subsets of patients with angina (10 with stable effort angina, 36 with resting angina [24 in an active phase and 12 in an inactive phase], and five with Prinzmetal's variant angina) and in 41 control subjects of equivalent age and risk factors. Left ventricular end-diastolic pressure, ejection fraction, extent of coronary angiographic lesions, and baseline PVR were not significantly different among the various patient groups. In all patient groups, except those with variant angina, the cold pressor test resulted in a higher increase in PVR than in the control subjects (p less than .001 for all groups). In patients with variant angina the vasoconstrictor response was increased only in proximity (about 1 hr) to ischemic attacks. In patients with active resting angina the vasoconstrictor response was on the average four times longer than that in patients with effort angina and with inactive resting angina (p less than .001). This exaggerated vasoconstrictor response was associated with elevated TxA2 resting levels in plasma and with increased TxA2 synthesis after the cold pressor test. A linear relationship was found between the area of the vascular response and the area of TxA2 production after the cold pressor test in patients with active resting angina (r = .87, p less than .001). The increased TxA2 synthesis and the inappropriate increase of peripheral vascular response to sympathetic stimulation revert back to normal in the inactive phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Accurate noninvasive quantification of stenotic aortic valve area by Doppler echocardiography.
Authors: Zoghbi W A , Farmer K L , Soto J G , Nelson J G , Quinones M A
Published: June 2011

Laminar flow through a conduit is equal to the mean velocity times the cross-sectional area of the orifice. Therefore, volume is equal to the time-velocity integral multiplied by the cross-sectional area. In aortic stenosis, flow in the stenotic jet is laminar and the aortic valve area should be equal to the volume of blood ejected through the valve divided by the time-velocity integral of the aortic jet velocity recorded by continuous-wave Doppler echocardiography. To test whether this concept can be used to accurately determine aortic valve area noninvasively by the Doppler method, 39 patients (age 35 to 82 years, mean 63) underwent pulsed Doppler combined with two-dimensional echocardiography for measurement of stroke volume at the aortic, pulmonic, and mitral anulus as well as continuous-wave Doppler recording of the aortic jet. Aortic valve area determined at cardiac catheterization by the Gorlin equation ranged between 0.4 and 2.07 cm2 (mean 0.89 +/- 0.45). Doppler-derived valve area, determined with the stroke volume value from either the aortic, pulmonic, or mitral anulus, correlated well with the area determined at cardiac catheterization (r = .95, .97, and .96, respectively). A simplified method for measuring aortic valve area derived as the cross-sectional area of the aortic anulus times peak velocity just proximal to the aortic valve divided by peak aortic jet velocity correlated well with measurements obtained at cardiac catheterization (r = .94). An excellent separation between critical and noncritical aortic stenosis was seen using either one of the Doppler methods.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in cross-sectional area of the coronary lumen in the six months after angioplasty: a quantitative analysis of the variable response to percutaneous transluminal angioplasty.
Authors: Johnson M R , Brayden G P , Ericksen E E , Collins S M , Skorton D J , Harrison D G , Marcus M L , White C W
Published: June 2011

Although immediate and late changes in coronary stenoses after percutaneous transluminal coronary angioplasty (PTCA) have been reported, most investigators have employed qualitative or semiquantitative techniques to analyze the angiograms. Such data is not optimal because of considerable interobserver variability and the use of relative instead of absolute changes in lesion geometry. Analysis is further compounded by the indistinct edges that characterize coronary lesions immediately after angioplasty. To quantify the changes in minimal cross-sectional area (MCSA) of the coronary lumen that occur during and after PTCA, we analyzed the angiograms of 23 patients before PTCA, immediately after PTCA, and at 7.2 +/- 3.0 (mean +/- SD) months follow-up using two computer-assisted methods of angiographic analysis--quantitative coronary angiography (QCA) and videodensitometry (VID). QCA provides an absolute measure of the area of the lumen; VID is a nongeometric method that is not dependent on exact border recognition. Based on these quantitative methods, we found that successful angioplasty is associated with about a three-fold increase in the MCSA of the lesion (from 1.0 to 3.2 mm2). This area is, however, well below normal and is less than half of the average MCSA of the inflated dilating balloon. Analysis of follow-up angiograms demonstrated that eight of 23 patients had a substantial late increase in the MCSA of the lesion (from 2.7 to 4.1 mm2) after the angioplasty procedure. Clinical, hemodynamic, and angiographic characteristics immediately after PTCA were not predictive of MCSA of the lumen at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
Internal cardiac defibrillation in man: pronounced improvement with sequential pulse delivery to two different lead orientations.
Authors: Jones D L , Klein G J , Guiraudon G M , Sharma A D , Kallok M J , Bourland J D , Tacker W A
Published: June 2011

Wider applicability of an implantable automatic defibrillator depends on achieving internal cardiac defibrillation consistently with the lowest possible energy. In animal studies, we have found that the cardiac defibrillation threshold could be reduced when sequential shocks separated in time and spacially arranged were delivered to the heart. We compared internal cardiac defibrillation using a single pulse shock delivered through an intravascular catheter with this new method for internal cardiac defibrillation in patients undergoing cardiac surgery for the correction of arrhythmias. For the single pulse shock and the first pulse of the sequential pulse shock, current was passed through an intravascular catheter with the catheter cathode at the apex of the right ventricle and the anode at the superior vena cava-atrial junction region. The second pulse of the sequential pulse countershock was delivered between the catheter cathode in the right ventricular apex and an oval plaque electrode secured on the laterobasal left ventricular epicardium as anode. With the single pulse alone for shock delivery, 12 patients could be defibrillated with an average of 20.1 +/- 16.8 J, with a corresponding leading-edge peak voltage and current of 836 +/- 319 V and 9.4 +/- 4.5 A, respectively. However, two of the patients could not be defibrillated with energies below 50 J. With the sequential pulse shock delivery, a significant reduction in all values were recorded. Mean total energy for defibrillation averaged 7.7 +/- 6.0 J. Leading-edge peak voltage and current from the catheter averaged 430 +/- 148 V and 5.0 +/- 2.8 A, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Exercise-induced regional dysfunction with subcritical coronary stenosis.
Authors: Lee J D , Tajimi T , Guth B , Seitelberger R , Miller M , Ross J
Published: June 2011

The hypothesis was tested that regional myocardial contractile dysfunction can detect subtle regional coronary blood flow maldistribution induced by exercise. In seven dogs, left ventricular pressure (micromanometer), regional systolic wall thickening (WTh, sonomicrometry), and myocardial blood flow (MBF, microspheres) were measured when mild degrees of coronary artery stenosis were produced during treadmill exercise. During exercise without coronary stenosis, WTh increased by 21 +/- 12% (SD), and transmural MBF increased uniformly. In each dog, two levels of coronary stenosis were produced during exercise by adjusting the coronary hydraulic cuff: (1) St-Ex I, where WTh during exercise failed to increase significantly (average change 0 +/- 7%), and (2) St-Ex II, where WTh during exercise decreased moderately from the resting control value (average -20 +/- 8%). In the potentially ischemic zone coronary hyperemia occurred with each run: resting subendocardial MBF was 1.09 +/- 0.30 mg/g/min, and it was 3.04 +/- 0.83 during control exercise, 2.48 +/- 0.75 during St-Ex I, and 1.55 +/- 0.59 ml/g/min during St-Ex II (p less than .01 compared with control exercise and control area). The subendocardial-subepicardial blood flow ratio fell from 1.32 +/- 0.27 during control exercise to 1.07 +/- 0.20 (p less than .05) during St-Ex I, and to 0.64 +/- 0.15 (p less than .01) with St-Ex II. Changes in the subendocardial electrogram and reactive hyperemia occurred more consistently during St-Ex II than St-Ex I. Thus, failure of regional function to increase during exercise detected slight maldistribution of regional MBF, whereas reduction of regional function during exercise of 10% or more below the resting value was a reliable marker of a regional flow defect and was always associated with other evidence of ischemia. Therefore, regional dysfunction during exercise can detect subcritical but functionally significant coronary stenosis, which may allow regional wall motion to be used for detecting coronary artery disease at a relatively early stage.
Vulnerability to ventricular arrhythmia: assessment by mapping of body surface potential.
Authors: Gardner M J , Montague T J , Armstrong C S , Horacek B M , Smith E R
Published: June 2011

It is now well established that the vulnerability of the ventricular myocardium to repetitive dysrhythm increases in the presence of greater than normal disparity local recovery times. Local recovery is reflected in the electrocardiographic waveform as an area of the ventricular deflection (QRST time integral), and thus disparate ventricular recovery may be manifested in the body surface distribution of this quality. To assess this possibility, we obtained simultaneous 120-lead electrocardiograms from both the anterior and posterior torso in 140 subjects (ages 8 to 75) grouped as follows: group A, 97 normal subjects; group B, 16 patients resuscitated from ventricular fibrillation or sustained ventricular tachycardia; and group C, 27 patients 6 to 12 months after myocardial infarction but without clinically significant arrhythmia. In each subject, the QRST integral was evaluated for each lead and isointegral contour maps were plotted. A score was assigned to each map, based on the number of extrema; each maximum or minimum scored one point, with the exception of simultaneously occurring anterior and posterior minima on the right shoulder (frequently occurring in normal subjects), which scored together only one point. All but one group A subject had dipolar QRST integral maps (mean +/- SD score 2.11 +/- 0.2). Conversely, 10 of 16 (62.5%) group B patients had scores of 3 or more (mean 3.16 +/- 1.08; p less than .01 vs group A). Group C patients had intermediate values, with eight of 27 (29.6%) scoring 3 or more (mean 2.46 +/- 83); this was less than in group B (p less than .01), but more (p less than .05) than in group A.(ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy of an automated external defibrillator in the management of out-of-hospital cardiac arrest: validation of the diagnostic algorithm and initial clinical experience in a rural environment.
Authors: Stults K R , Brown D D , Kerber R E
Published: June 2011

Automatic external defibrillators (AEDs) may have advantages over manual defibrillation in managing prehospital cardiac arrest, particularly in rural communities. We conducted a two-part evaluation of a commercially available AED. We first established the diagnostic accuracy of the AED's rhythm recognition algorithm by challenging it with 205 cardiac arrest rhythms previously recorded from actual patients in the field. The AED demonstrated 100% specificity and 92% sensitivity for ventricular fibrillation (VF) in this nonclinical setting. We then compared the clinical efficacy of AEDs in 18 small communities (study group) with that of manual defibrillation in 18 additional communities (control group) of similar size. Ambulance technicians using manual defibrillators correctly diagnosed VF more frequently than the AEDs (98% vs 83%; p less than .025). Specificity for VF was similar in the two groups (100% for AEDs vs 94% for technicians; p greater than .10). AEDs were able to deliver shocks more quickly than was possible with the manual defibrillators (1.56 vs 2.77 min; p less than .001). The ability of the AEDs to terminate VF was excellent, converting VF in 28 of 29 (97%) patients to some other rhythm compared with only 37 of 53 (70%) patients in the control group (p less than .01). Hospital admission and discharge rates were similar for the two groups. Ten of the 35 (29%) patients managed with AEDs achieved admission and six (17%) were ultimately discharged. In the control group 17 of 53 (33%) patients with VF were admitted and seven (13%) were discharged (p less than .75). AEDs are an effective alternative to manual defibrillation in small communities.
Effect of propranolol on myocardial ischemia occurring during acute coronary occlusion.
Authors: Feldman R L , MacDonald R G , Hill J A , Limacher M C , Conti C R , Pepine C J
Published: June 2011

In 16 patients undergoing angioplasty of the left anterior descending coronary artery, the clinical, electrocardiographic, and hemodynamic effects of short-term intravenous nonselective beta-adrenergic blockade with propranolol (0.1 mg/kg) were assessed during temporary occlusion of the artery. Myocardial ischemia during coronary occlusion was prevented, delayed in onset, or diminished in magnitude by propranolol in 10 of the 16 patients. Propranolol decreased values for indexes of myocardial oxygen demand, such as heart rate and blood pressure and their product, in all patients. Surprisingly, in patients who derived clinical benefit, propranolol did not change indexes of myocardial oxygen supply to the left ventricular region perfused by the occluded artery. For example, great cardiac vein flow (40 +/- 15 to 41 +/- 17 ml/min, p = NS) and coronary collateral resistance (2.1 +/- 1.0 to 2.1 +/- 1.1 mm Hg/ml/min, p = NS) were unchanged. In contrast, a worsening of supply occurred in patients who were not benefited: great cardiac vein flow (50 +/- 10 to 39 +/- 6 ml/min, p less than .05) decreased and coronary collateral resistance (1.6 +/- 0.5 to 2.0 +/- 0.6 mm Hg/ml/min, p less than .05) increased. Information obtained from this study demonstrates the value of this new experimental preparation in helping assess potential clinical effectiveness of drug interventions during the initial phase of acute coronary occlusion and providing insight into the mechanisms of drug effect.
Effects of long-term therapy with oral ibopamine on resting hemodynamics and exercise capacity in patients with heart failure: relationship to the generation of N-methyldopamine and to plasma norepinephrine levels.
Authors: Rajfer S I , Rossen J D , Douglas F L , Goldberg L I , Karrison T
Published: June 2011

N-Methyldopamine (epinine), one of the few modifications of the dopamine (DA) molecule that retains agonist activity at the DA1 receptor, was administered orally as the diisobutyric ester, ibopamine (100, 200, and 300 mg), to 15 patients with congestive heart failure. An increase in cardiac index and decline in systemic vascular resistance was observed with each dose, and these hemodynamic effects persisted for 3 to 6 hr. Small transient increments in right atrial and pulmonary capillary wedge pressures occurred 0.5 hr after ingestion of 200 and 300 mg of ibopamine, but these pressures returned to baseline or lower levels within 30 min. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of epinine peaked 0.5 hr after administration of drug and then declined to minimal levels at 3 hr. Ten patients enrolled in a trial to evaluate the efficacy of long-term therapy with ibopamine; after 8 weeks of treatment, the initial hemodynamic responses to the drug were attenuated and no significant improvement in oxygen uptake at peak exercise was observed. A decline in plasma norepinephrine concentrations, which could be attributed to activation of alpha 2-adrenoceptors and/or DA2 receptors on sympathetic nerves, was observed after initial administration of ibopamine and persisted after long-term drug ingestion; no long-term hemodynamic benefit could be ascribed to the reduction in sympathetic activity.
Pulsed Doppler echocardiographic assessment of the pulmonary venous pathway after the Mustard or Senning procedure for transposition of the great arteries.
Authors: Smallhorn J F , Gow R , Freedom R M , Trusler G A , Olley P , Pacquet M , Gibbons J , Vlad P
Published: June 2011

Pulsed Doppler evaluation of pulmonary venous flow was performed in three groups of patients who had undergone either a Mustard or Senning procedure. Group I consisted of 43 patients in sinus rhythm who had undergone the Mustard procedure 9 months or more before the Doppler examination and 16 who were evaluated immediately after surgery. Group II consisted of 12 patients in sinus rhythm who had undergone the Senning procedure 9 months or more before the Doppler evaluation. Group III consisted of eight patients with mid baffle obstruction of the pulmonary venous atrium and seven with isolated stenosis of the pulmonary vein of which all but one had previously had associated mid baffle obstruction. In those without obstruction, the pulmonary venous flow pattern mirrored the left atrial pressure trace, with peak forward flow occurring during the x and y descent. Obstruction produced a specific high-velocity turbulent pattern, whether at the mid baffle or pulmonary venous level. This technique provides reliable noninvasive information about pulmonary venous flow after the Mustard or Senning procedure.
Partial reversal of asymmetry in microvessel neurochemical changes after ischemia by corpus callosum section.
Authors: Magnoni M S , Kobayashi H , Govoni S , Battaini F , Pasinetti G , Trabucchi M
Published: June 2011

Common carotid occlusion in the rat significantly decreases the density of beta-adrenergic receptors in preparations of microvessels obtained from ipsilateral and contralateral cerebral cortices. The disruption of nerve pathways connecting the hemispheres (callosal transection) partially reverses the effect of common carotid occlusion on beta-adrenergic receptor density in capillaries of the contralateral cortex. In addition, the destruction of the central noradrenergic system by intraventricular injection of 6-hydroxydopamine abolishes the effect of ischemia on capillary beta-adrenergic receptor function in both hemispheres. The results suggest that beta-adrenergic receptors located on microvessels are partially regulated by neuronal pathways and that focal ischemia induces neurochemical and functional changes in remote areas of the brain.
Sympathetic and periodic vagal influences on antegrade and retrograde conduction through the canine atrioventricular node.
Authors: Wallick D W , Stuesse S L , Masuda Y
Published: June 2011

Concurrent stimulation of the parasympathetic and sympathetic branches of the autonomic nervous system causes a diminished sympathetic response at high levels of vagal activity. This "accentuated antagonism" has been demonstrated for cardiac chronotropic, inotropic, and dromotropic responses. The effect on conduction was demonstrated with tonic stimulation of the vagus nerve. However, normally the vagus nerve fires periodically at certain times in the cardiac cycle. Thus, we have studied whether a similar interaction exists in the modulation of atrioventricular condition when short bursts of vagal stimulation were placed in various portions of the cardiac cycle. Anesthetized open-chest mongrel dogs were instrumented for stimulation of the cervical vagi and stellate ganglia when the heart was paced. We determined the relationship between cardiac cycle length, direction of action potential propagation, and levels of sympathetic and vagal activation and their effects on atrioventricular conduction times. All of the factors investigated, namely levels of vagal and stellate stimulation, pacing intervals, and direction of propagation of action potentials, affected atrioventricular conduction times. Furthermore, the vagal effect was greater at short cardiac cycle lengths. When bursts of vagal stimulation were timed to result in maximal or minimal prolongation of atrioventricular conduction, no significant effects of sympathetic-parasympathetic interaction on atrioventricular conduction times were apparent. However, an analysis of the differences in prolongation of atrioventricular conduction with periodic vagal stimulation revealed that a significant sympathetic-vagal interaction existed for these differences. Thus, autonomic neurotransmitters differentially affect cardiac conduction times depending on time of application of the stimulus.
Comparison of the defibrillation threshold and the upper limit of ventricular vulnerability.
Authors: Chen P S , Shibata N , Dixon E G , Martin R O , Ideker R E
Published: June 2011

To examine the relationship between the defibrillation threshold and the strength of shocks that induce ventricular fibrillation during the vulnerable period, we determined the defibrillation threshold in 22 open-chest dogs using epicardial defibrillation electrodes with the cathode at the ventricular apex and the anode at the right atrium. We also determined whether there was an upper limit of shock strength that induces fibrillation in the vulnerable period by giving shocks of various energy through these same electrodes during the repolarization phase of paced rhythm. The above determinations were also made with the anode at the ventricular apex and the cathode at the right atrium in eight of the dogs and with the cathode at the ventricular apex and the anode at the left atrium in another eight of the dogs. In all dogs for all electrode configurations, there was an upper limit to the shock strength that induced ventricular fibrillation during the vulnerable period. Depending on the electrode combination, this upper limit of ventricular vulnerability either was not significantly different from or was slightly lower than the defibrillation threshold. The correlation coefficient between the two was highly significant for all three electrode configurations. These results support the hypothesis that successful defibrillation with epicardial electrodes requires a shock strength that reaches or exceeds the upper limit of ventricular vulnerability and that shocks slightly lower than the defibrillation threshold fail because they reinitiate ventricular fibrillation by stimulating portions of the myocardium during their vulnerable period.
Pulmonary vascular effects of hydralazine in a canine preparation of pulmonary thromboembolism.
Authors: Ducas J , Girling L , Schick U , Prewitt R M
Published: June 2011

Pulmonary arterial pressure (PAP)-flow coordinates were obtained in 14 anesthetized dogs before and after pulmonary hypertension was induced with autologous blood clots. Cardiac output (CO) was altered by systemic arteriovenous fistulas. The PAP-CO coordinates were always rectilinear. Before emboli, the mean vascular closing or outflow pressure (the pressure intercept of the PAP-CO line) was 8.8 +/- 2.1 (SD) mm Hg. Emboli increased PAP (15.1 +/- 1.6 to 36.5 +/- 3.5 mm Hg; p less than .001) and decreased CO (3.8 +/- 0.6 to 2.4 +/- 0.8 liters X min-1; p less than .001). Incremental resistance (the slope of the PAP-CO line) only increased slightly. On the other hand, the marked increase in PAP was predominantly due to an increase in effective outflow pressure (from 8.8 +/- 2.1 to 28.6 +/- 3.6; p less than .001). Hydralazine was administered in a dose sufficient to double CO. This did not affect PAP and caused an inconsistent and small decrease in incremental resistance. However, a consistently significant decrease in effective outflow pressure, averaging 23%, was observed. In this canine preparation of pulmonary hypertension the predominant effect of hydralazine appears to be a decrease in the mean vascular closing or outflow pressure.
Is the aorta truly dextroposed in tetralogy of Fallot? A two-dimensional echocardiographic answer.
Authors: Isaaz K , Cloez J L , Marçon F , Worms A M , Pernot C
Published: June 2011

The embryogenesis of tetralogy of Fallot is still much debated. In particular, the dextroposition of the aorta is not considered by all pathologists as a genuine abnormality in this congenital heart disease but rather as a false impression due to an exaggeration of the normal overriding caused by dilatation of the aorta secondary to abnormal hemodynamics. We used two-dimensional echocardiography to examine the spatial position of the aortic root in 22 patients with tetralogy of Fallot (aged 5 days to 24 years, mean 6.4 years) and in 23 normal subjects (aged 1 month to 27 years, mean 7.6 years). Using the parasternal short-axis view, we determined the percent rightward displacement of the aortic root in relation to the plane of the atrial septum, and the relationship between the aortic cusps and the atrial septum. We measured the value of the angle luminal diameter, which was defined as the angle between the plane of the atrial septum and the plane of the left coronary-noncoronary commissure and leaflet appositional plane. In the control group, the aortic root was displaced to the right by only 23.6 +/- 7.6%; the atrial septum crossed the posterior aspect of the aortic root at the middle (n = 19) or at the right half of the posterior cusp (n = 4), and the angle luminal diameter had a value of 43.3 +/- 8.8 degrees. In the 22 patients with tetralogy, the percent rightward shift of the aortic root was augmented to 55.5 +/- 9% (p less than .001) and the atrial septum was related to the posterior commissure in 14 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitral regurgitation: relationship of noninvasive descriptors of right and left ventricular performance to clinical and hemodynamic findings and to prognosis in medically and surgically treated patients.
Authors: Hochreiter C , Niles N , Devereux R B , Kligfield P , Borer J S
Published: June 2011

To determine objective predictors of survival, 53 patients with chronic, hemodynamically severe mitral regurgitation underwent rest and exercise radionuclide cineangiography, echocardiography, treadmill exercise testing, and ambulatory electrocardiographic monitoring before prospective (average 30 month) follow-up. At entry, symptom status correlated best with radionuclide-based right ventricular ejection fraction (RVEF) and left atrial size, while treadmill exercise tolerance correlated best with RVEF during exercise (r = .48, p less than .005). Correspondingly, in 23 patients who underwent cardiac catheterization, pulmonary arterial systolic and wedge pressures were significantly inversely related to RVEF. On the 24 hr ambulatory electrocardiogram, nonsustained ventricular tachycardia was present in 29% of patients, most frequently when both RVEF and left ventricular ejection fraction (LVEF) were subnormal (p = .03 vs other patients). Since entry, 35 patients have been managed without surgery for 9 to 57 months (average 28); three of these who subsequently underwent operation also are among the 21 patients who have undergone mitral valve replacement (MVR). During the average 28 months of observation under medical treatment five of 35 nonoperated patients have died; all five were among the six nonoperated patients with RVEFs of 30% or less at entry, a descriptor that significantly identified those at high mortality risk (p less than .0001 vs patients with RVEFs greater than 30%). All five also were among the eight nonoperated patients with LVEFs of 45% or less (lower limit of normal), a descriptor that also significantly predicted mortality. Three of the 21 patients who underwent surgery have died, all late after MVR. Among operated patients, only age was a predictor of postoperative survival. A trend toward improved survival was found in the patients with depressed right or left ventricular ejection fraction who underwent surgery compared with those who did not.