bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accentuated vagal antagonism of beta-adrenergic effects on ventricular repolarization. Evidence of weaker antagonism in hostile type A men.
Authors: Fukudo S , Lane J D , Anderson N B , Kuhn C M , Schanberg S M , McCown N , Muranaka M , Suzuki J , Williams R B 
Published: June 2012

BACKGROUND
Prior research has suggested a weaker parasympathetic antagonism of sympathetic effects on the heart in type A (coronary-prone) men. To confirm this phenomenon and extend our understanding of it, we investigated the effects of prior muscarinic blockade on the electrocardiogram T wave and other cardiovascular and neuroendocrine responses to isoproterenol in type A and type B (non-coronary-prone) men.

METHODS AND RESULTS
Responses to two 5-minute intravenous isoproterenol infusions (0.01 micrograms/kg/min and 0.02 micrograms/kg/min) were evaluated in six type A and six type B men after pretreatment with either dextrose placebo or atropine (1.2 mg). Atropine significantly potentiated T wave attenuation in the recovery period after isoproterenol infusion (0.30 +/- 0.07 mV) compared with placebo (0.54 +/- 0.09 mV, p less than 0.001). Atropine also potentiated the heart rate increase to isoproterenol (39 +/- 3 beats per minute versus 20 +/- 2 beats per minute after placebo). Atropine enhanced decreases in systolic, diastolic, and mean arterial pressures as well as pulse pressure to isoproterenol. Atropine enhancement of many of these responses was increased among subjects with high scores on various hostility/anger scales. Isoproterenol alone produced greater T wave attenuation in type A than in type B men. However, atropine enhancement of T wave attenuation and blood pressure falls by isoproterenol was present only in type B men.

CONCLUSIONS
These findings indicate that there is accentuated parasympathetic antagonism of T wave attenuation and blood pressure responses induced by beta-adrenergic stimulation. Relative weakness of this antagonism of sympathetic effects on the heart in hostile type A individuals may contribute to their higher coronary disease risk.
Investigation of a hemodynamic basis for syncope in hypertrophic cardiomyopathy. Use of a head-up tilt test.
Authors: Gilligan D M , Nihoyannopoulos P , Chan W L , Oakley C M 
Published: June 2012

BACKGROUND
Syncope and sudden death in hypertrophic cardiomyopathy may have a hemodynamic basis. The presence of a small ventricular cavity with high intracavity pressures may activate left ventricular baroreceptors and cause reflex hypotension as described in other populations with syncope.

METHODS AND RESULTS
To investigate this potential mechanism of syncope in hypertrophic cardiomyopathy, we studied 17 patients with a history of syncope (syncopal), 19 without syncope (nonsyncopal), and nine normal control subjects by using a head-up tilt test. Head-up tilt at 60 degrees for 45 minutes was followed by 10-minute tilts during incremental doses of isoprenaline. Heart rate, blood pressure, and two-dimensional and Doppler echocardiography were monitored throughout. On tilting, hypertrophic cardiomyopathy patients showed a decline in mean arterial pressure of -5 +/- 6 mm Hg (p less than 0.001) compared with no change in control subjects (0.2 +/- 6 mm Hg, p = 0.9). Left ventricular outflow tract velocity decreased on tilting in control subjects (-8 +/- 6 cm/sec, p = 0.004) but increased in the syncopal and nonsyncopal patients (20 +/- 50 cm/sec, p = 0.05). Reflex hypotension with or without bradycardia, associated with syncope or presyncope, was induced in seven syncopal patients, two nonsyncopal patients, and two control subjects (p = 0.05). The early response to tilt in these subjects was characterized by maintenance of blood pressure but a greater increase in left ventricular fractional shortening than in the other subjects (10 +/- 8% versus 1 +/- 1%, p = 0.002). The onset of hypotension was associated with a trend toward further decreases in left ventricular diameters, outflow tract velocity, and transmitral flow velocities. In the remaining patients who had a negative test, transient hypotension (systolic pressure less than 100 mm Hg) occurred in seven syncopal patients and three nonsyncopal patients compared with none of the control subjects (p = 0.01). In total, hypotension was demonstrated in 82% of syncopal patients compared with 26% of nonsyncopal patients and 22% of control subjects (p = 0.001).

CONCLUSIONS
Patients with hypertrophic cardiomyopathy and a history of syncope frequently display hypotension during head-up tilt. In some cases, sudden hypotension occurs and is usually associated with bradycardia and a reduced cavity size, findings compatible with activation of a ventricular baroreflex. In other cases, transient hypotension occurs and could be explained by an impairment of baroreceptor function. These mechanisms may contribute to the occurrence of syncope in daily life.
A quantitative analysis of use-dependent ventricular conduction slowing by procainamide in anesthetized dogs.
Authors: Villemaire C , Savard P , Talajic M , Nattel S 
Published: June 2012

BACKGROUND
Use-dependent effects of antiarrhythmic drugs on phase 0 sodium current result in rate-dependent conduction slowing with important potential clinical consequences. The purpose of the present study was to determine whether state-dependent interactions of procainamide with sodium channels can be analyzed based on conduction changes in vivo.

METHODS AND RESULTS
Procainamide infusions were used to produce stable drug concentrations causing greater than or equal to 25% conduction slowing at a basic cycle length (BCL) of 300 msec in morphine/chloralose-anesthetized dogs with formalin-induced atrioventricular block. Computer-based epicardial activation mapping was applied to assess the time course and pattern of conduction over a wide range of BCLs before and after drug administration. Action potential duration was measured from recordings of monophasic action potentials. The onset and steady-state values of fractional sodium channel block estimated from conduction changes were fitted to equations obtained from a stepwise exponential analysis. The rate constant for the onset of block (lambda *) decreased, as predicted, with decreasing cycle length. The slope of the relation between lambda * and recovery time at each BCL averaged 0.29 +/- 0.03 sec-1, resulting in a calculated recovery time constant (3.4 seconds) similar to values previously obtained by direct measurement. Estimates of binding and unbinding rate constants for the sodium channel during the action potential plateau and after repolarization were of the same order as previous results obtained using microelectrode methods in vitro.

CONCLUSIONS
Use-dependent conduction changes produced by procainamide in vivo closely follow the predictions of mathematical models of drug-channel interactions, and underlying kinetic interactions with the sodium channel inferred from conduction changes agree with previous, more direct observations. These results support the relevance of basic concepts about antiarrhythmic drug actions on sodium channels for understanding drug effects on conduction in vivo and advance analytical tools that can be used to explore the latter in humans.
Intraluminal ultrasound imaging through a balloon dilation catheter in an animal model of coarctation of the aorta.
Authors: Rothman A , Ricou F , Weintraub R G , Crowley R , Arcangeli R , Shiota T , Zhang J , Sahn D J 
Published: June 2012

BACKGROUND
Controversy still exists over the optimal balloon size, extent of vascular disruption, and long-term results of balloon dilation therapy for coarctation of the aorta. Intravascular ultrasound imaging has been used in patients with coronary artery disease to provide further insight into the anatomy of atherosclerotic lesions and the results of angioplasty and atherectomy. Initial observations of the results of balloon dilation of coarctations with intravascular ultrasound imaging have shown prominent dissections of the inner vascular layers that are often not detected by angiography. The purpose of this study was to test a new transballoon catheter ultrasonic imaging system capable of on-line direct visualization of lumen diameter and vessel wall structure for imaging before, during, and after dilation in an acute animal model of aortic coarctation.

METHODS AND RESULTS
Abdominal aortic coarctations were created surgically in three 14-19-kg mongrel dogs by using Teflon gauze ties. The 6.8F ultrasound balloon catheter was placed percutaneously in the right femoral artery through a 9F sheath. Ultrasound imaging allowed measurement of the coarctation diameter, characterization of the vessel wall structure, localization of the stenosis, and placement of the midportion of the balloon at the narrowest area. Imaging through the balloon was performed through several dilations (five to eight per animal), and after balloon deflation, it provided information on postdilation diameter, intimal tears, long-segment dissections, and intramural thrombi, findings that were confirmed at postmortem examination.

CONCLUSIONS
The results of this study demonstrate that imaging with a new intraballoon ultrasound device is feasible during inflation to therapeutic dilation pressures; it allows visualization of the changes in diameter and vascular wall structure after serial dilations without having to recross the obstructed area. Adaptation to larger balloon sizes and lower frequencies should make this system applicable to interventional catheterizations in patients with congenital cardiac and vascular lesions.
Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis.
Authors: Goto M , Flynn A E , Doucette J W , Kimura A , Hiramatsu O , Yamamoto T , Ogasawara Y , Tsujioka K , Hoffman J I , Kajiya F 
Published: June 2012

BACKGROUND
Nitroglycerin is effective in relieving myocardial ischemia; however, intracoronary nitroglycerin often fails to relieve angina and has been reported to have deleterious effects on subendocardial blood flow. To understand the mechanisms involved, we evaluated the direct effect of nitroglycerin on coronary circulation of the ischemic hearts.

METHODS AND RESULTS
We measured the phasic pattern of intramyocardial coronary arterial flow with an 80-channel, 20-MHz pulsed Doppler ultrasound flowmeter under moderate to severe coronary artery stenosis (distal perfusion pressure approximately 45 mm Hg group 1, n = 6) and transmyocardial blood flow distribution using radioactive microspheres while maintaining coronary pressure at a low constant level (40 mm Hg, group 2, n = 6). In anesthetized open-chest dogs, the left main coronary artery was perfused directly from the right carotid or femoral artery. In this bypass circuit, pressure was controlled with an occluder or a reservoir was connected to the circuit. In group 1, the systolic and diastolic pressures distal to the stenosis decreased significantly after intracoronary administration of nitroglycerin at maximal coronary flow from 66.5 +/- 18.5 to 56.5 +/- 13.8 mm Hg (p less than 0.01) and from 36.6 +/- 14.4 to 27.5 +/- 8.9 mm Hg (p less than 0.01), respectively. The phasic pattern of the septal artery flow was predominantly diastolic and was characterized by systolic reverse flow even in the absence of stenosis. Coronary stenosis increased systolic reverse flow. Nitroglycerin increased diastolic forward flow (p less than 0.05) but augmented systolic reverse flow markedly (p less than 0.001). In group 2, nitroglycerin increased subepicardial flow (p less than 0.05) but failed to increase subendocardial flow. With the administration of nitroglycerin, the subendocardial-to-subepicardial flow ratio decreased significantly from 0.73 +/- 0.19 to 0.32 +/- 0.14 (p less than 0.01).

CONCLUSIONS
The increased systolic reverse flow after intracoronary administration of nitroglycerin may be closely related to failure of subendocardial blood flow to increase with increase subepicardial flow.
Exaggerated pressor response to treadmill exercise in chronic cocaine abusers with left ventricular hypertrophy.
Authors: Cigarroa C G , Boehrer J D , Brickner M E , Eichhorn E J , Grayburn P A 
Published: June 2012

BACKGROUND
Chronic cocaine abuse has been associated with a high prevalence of left ventricular hypertrophy (LVH) in normotensive individuals at rest. This study was conducted to determine whether chronic cocaine abusers with LVH would manifest an exaggerated pressor response to treadmill exercise.

METHODS AND RESULTS
Forty-nine normotensive chronic cocaine abusers underwent Bruce protocol treadmill exercise testing until they attained 85% maximum predicted heart rate. A peak exercise systolic blood pressure greater than or equal to 210 mm Hg was defined as abnormal. In addition, they underwent two-dimensional echocardiography and had left ventricular mass determined by the area-length method. LVH was defined as left ventricular mass greater than or equal to 105 g/m2 and a posterior wall thickness greater than or equal to 1.2 cm. Age- and race-matched control subjects also underwent echocardiography and exercise testing. Group differences in peak exercise blood pressure in cocaine abusers with LVH, cocaine abusers without LVH, and control subjects were assessed by ANOVA: Groups were similar concerning age, race, heart rate, resting blood pressure, body surface area, and exercise duration. LVH was present in 16 of 49 (33%) cocaine abusers and three of 30 (10%) control subjects (p = 0.02). Of the 16 cocaine abusers with LVH, 10 (63%) had peak exercise blood pressures greater than or equal to 210 mm Hg, and three others had exercise blood pressures of 200 mm Hg. Therefore, peak exercise systolic blood pressure was significantly higher in cocaine abusers with LVH than in all other groups (p = 0.0001).

CONCLUSIONS
Chronic cocaine abusers with LVH manifest an exaggerated pressor response to treadmill exercise. These data suggest that chronic cocaine abuse predisposes a subset of individuals to a heightened pressor response to a given sympathetic stimulus such as exercise and that this may contribute to the pathogenesis of LVH in chronic cocaine abusers.
Hemodynamic and reflex sympathetic control of transmural activation and rate of ventricular tachycardia in ischemic and hypertrophic ventricular myocardium of the dog.
Authors: Hopson J R , Martins J B 
Published: June 2012

BACKGROUND
A previous study found that the electrophysiological response to ischemia is altered in hypertrophic myocardium, resulting in prolonged transmural activation time (TAT) associated with induction of sustained monomorphic ventricular tachycardia. This study investigated the role of hemodynamics in modulating TAT and the cycle length of induced ventricular tachycardia (VT) in dogs with left ventricular hypertrophy (LVH).

METHODS AND RESULTS
Anesthetized open-chest dogs underwent 3 hours of uninterrupted circumflex coronary occlusion. During atrial drive, TAT was recorded between endocardial and epicardial bipolar pairs on the same multipolar plunge needle placed in nonischemic and ischemic zones, documented by triphenyltetrazolium chloride staining. TAT and VT induced by up to three extrastimuli were studied during hypertension (control), during normotension produced most frequently by nitroprusside infusion (3-6 micrograms/kg/min), and during further hypertension most frequently produced by phenylephrine infusion (1-5 micrograms/kg/min). Twenty-five dogs with chronic hypertension and LVH (group 1) produced by a single-kidney renal clamp mechanism and 15 control dogs were studied. In the latter, neither intervention altered TAT, and no VT was inducible. In group 1, however, nitroprusside reversibly prolonged TAT within the ischemic zone (mean +/- SEM, 31 +/- 3 to 34 +/- 3 msec, p less than 0.005) and cycle length of induced VT (204 +/- 19 to 240 +/- 17 msec, p less than 0.01). Phenylephrine reversibly shortened both TAT in the ischemic zone (33 +/- 2 to 28 +/- 2 msec, p less than 0.05) and cycle length of VT (219 +/- 17 to 165 +/- 11 msec, p less than 0.025). Cycle length of VT and TAT were dissociated from blood pressure elevation in two dogs with LVH; when blood pressure was elevated by sympathetic nerve stimulation, cycle length of VT and TAT were prolonged. In 11 dogs with LVH (group 2), prolongation of TAT with nitroprusside infusion was prevented by intravenous metoprolol (1.0 mg/kg). Of 12 dogs with LVH and inducible VT (group 3), seven still had VT inducible after metoprolol, but the cycle length of VT was still prolonged with nitroprusside infusion.

CONCLUSIONS
These results suggest that 1) TAT in acutely ischemic LVH was uniquely responsive to hemodynamic influences, an effect prevented by beta-blockade with metoprolol, and 2) the cycle length of VT was also uniquely regulated by hemodynamic influences but not blocked by metoprolol.
Different susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in humans. Effects of N-acetylcysteine administration.
Authors: Ghio S , de Servi S , Perotti R , Eleuteri E , Montemartini C , Specchia G 
Published: June 2012

BACKGROUND
Tolerance to the effects of organic nitrates develops rapidly during continuous exposure to these drugs; its main mechanism seems to be an intracellular sulfhydryl group depletion. However, the relative susceptibility to the development of nitroglycerin tolerance of the arterial or venous circulation in humans is still a matter of dispute.

METHODS AND RESULTS
Twenty patients with coronary artery disease underwent a continuous 24-hour nitroglycerin infusion followed by a bolus administration of N-acetylcysteine. Forearm blood flow (ml/100 ml/min) and venous volume (ml/100 ml) were measured by strain gauge plethysmography under control conditions, at the end of nitroglycerin titration, after 24-hour infusion, and after N-acetylcysteine; vascular resistance was calculated as mean cuff blood pressure divided by flow. After 24 hours of nitroglycerin infusion, the initial increase in venous volume was reduced 48% (p less than 0.01), whereas the acute effects on vascular resistance were not attenuated in the whole group. N-Acetylcysteine completely restored nitroglycerin venodilator effects in all 10 patients in whom attenuation of the venous effects was observed during the infusion period.

CONCLUSIONS
The data indicate that the susceptibility to the development of nitrate tolerance in humans is higher in the venous than in the arterial circulation, and that the sulfhydryl group donor N-acetylcysteine is extremely effective in reversing nitroglycerin tolerance in the venous circulation in humans.
Role of alpha 2-adrenoceptors in normal and atherosclerotic human coronary circulation.
Authors: Indolfi C , Piscione F , Villari B , Russolillo E , Rendina V , Golino P , Condorelli M , Chiariello M 
Published: June 2012

BACKGROUND
Experimental studies on the effects of alpha 2-adrenoceptors on regional coronary blood flow in normal and ischemic myocardium are highly controversial. A beneficial effect on regional ischemic myocardium has been demonstrated in different animal preparations with either alpha 2-adrenoceptor blockade or stimulation. Animal studies also demonstrated that postsynaptic alpha 2-adrenoceptors mediate vasoconstriction in coronary and femoral vascular beds. The aims of the study were 1) to investigate the effects of regional alpha 2-adrenoceptor stimulation on regional coronary blood flow in subjects with angiographically normal coronary arteries, 2) to assess the effect of alpha 2-adrenoceptor blockade on coronary circulation in control subjects, and 3) to examine the influence of atherosclerosis on coronary blood flow response to alpha 2-adrenoceptor blockade.

METHODS AND RESULTS
The effect of regional administration of BHT 933 (a selective alpha 2-adrenoceptor agonist) was studied in eight subjects with angiographically normal coronary arteries. The coronary blood flow velocity was measured using a subselective intracoronary 3F Doppler catheter and coronary diameter by quantitative coronary angiography. BHT 933 induced a reduction in coronary artery diameter from 2.5 +/- 0.6 mm to 1.8 +/- 0.4 mm (p less than 0.05) as well as in coronary blood flow velocity (from 6.4 +/- 0.9 cm/sec to 4.6 +/- 1.9 cm/sec, p less than 0.01). In some subjects, ST segment abnormalities occurred. In patients with angiographically normal coronary arteries (n = 6), the regional infusion of a selective alpha 2-adrenoceptor blocking agent after beta-blockade did not change coronary diameter or coronary blood flow velocity. In contrast, in patients with significant coronary stenoses (n = 6), regional infusion of an alpha 2-adrenoceptor blocking agent reduced regional coronary artery diameter (from 2.3 +/- 0.5 mm to 2.1 +/- 0.6 mm, p less than 0.01) as well as coronary blood flow velocity (from 5.8 +/- 0.8 cm/sec to 3.7 +/- 0.6 cm/sec, p less than 0.05); in addition, alpha 2-adrenoceptor blockade significantly increased coronary sinus plasma norepinephrine levels (from 300 +/- 144 pg/ml to 429 +/- 207 pg/ml, p less than 0.01).

CONCLUSIONS
The selective in vivo stimulation of alpha 2-adrenoceptors produces a reduction in coronary blood flow and diameter in humans with angiographically normal coronary arteries. alpha 2-Adrenergic blockade does not change coronary blood flow in subjects with angiographically normal coronary arteries (suggesting no resting alpha 2-adrenergic vasoconstrictor tone), whereas in patients with coronary artery stenosis, regional coronary blood flow decreases after alpha 2-receptor blockade. Finally, our data also suggest that alpha 2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the human heart.
Failure of an implantable cardioverter-defibrillator to redetect ventricular fibrillation in patients with a nonthoracotomy lead system.
Authors: Jung W , Manz M , Moosdorf R , Lüderitz B 
Published: June 2012

BACKGROUND
Shock delivery of an implantable defibrillator may cause a change in the amplitude of endocardial electrograms and impair the detection of ventricular fibrillation. Thus, the effects of shock discharges on the amplitude of endocardial electrograms were evaluated in five patients undergoing implantation of a cardioverter-defibrillator in combination with a new nonthoracotomy lead system.

METHODS AND RESULTS
At implant, bipolar endocardial electrograms were recorded before each shock application, during ventricular fibrillation, during redetection of ventricular fibrillation in case the applied shock was ineffective, and at intervals of 5, 10, 20, 30, 60, and 120 seconds after each shock delivery. The amplitude of the endocardial electrograms decreased from 10.5 +/- 3.8 mV during sinus rhythm to 6.3 +/- 1.9 mV during initial ventricular fibrillation and declined to 2.2 +/- 1.3 mV during redetection of ventricular fibrillation. After successful termination, the following bipolar electrograms could be obtained at the predetermined intervals: 1.9 +/- 1.2 mV, 3.1 +/- 1.8 mV, 4.5 +/- 1.9 mV, 6.5 +/- 2.9 mV, 9.5 +/- 3.3 mV, and 10.4 +/- 3.8 mV. At predischarge testing, failure of redetection of ventricular fibrillation could be documented in two patients, requiring rescue external defibrillation in both cases to restore sinus rhythm.

CONCLUSIONS
These findings demonstrate that the implantable cardioverter-defibrillator did not ensure reliable redetection of ventricular fibrillation in patients using the implanted nonthoracotomy lead system. Thus, the potential risk of sudden cardiac death may persist in these patients despite defibrillator therapy.