bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelin production in pulmonary circulation of patients with mitral stenosis.
Authors: Yamamoto K , Ikeda U , Mito H , Fujikawa H , Sekiguchi H , Shimada K 
Published: June 2012

BACKGROUND
Although plasma endothelin concentrations are elevated in patients with pulmonary hypertension, the precise sites of endothelin production have not been defined. We investigated the endothelin production in the pulmonary circulation of patients with mitral stenosis and its effects on pulmonary vascular tone.

METHODS AND RESULTS
We measured plasma concentrations of endothelin-1, angiotensin II, and thrombomodulin in blood samples obtained from the right and left atria of 10 consecutive patients with rheumatic mitral stenosis (mean age, 55 years; range, 39 to 68) who were undergoing percutaneous mitral valvuloplasty. Plasma levels of endothelin-1 were significantly higher in the left atrium than in the right atrium (3.25 +/- 0.45 versus 2.53 +/- 0.36 pg/mL, mean +/- SE, P < .001). The increased plasma endothelin-1 level in the left atrium, which reflected endothelin-1 production in the pulmonary circulation, was correlated with mean pulmonary artery pressure (r = .65, P = .04), mean pulmonary arterial wedge pressure (r = .67, P = .03), total pulmonary resistance (r = .68, P = .03), and 1/mitral valve area (r = .85, P = .002) but not with pulmonary vascular resistance (r = .04, P = .91). There were no significant differences in plasma levels of angiotensin II and thrombomodulin between the right and left atria (angiotensin II, 16.40 +/- 3.08 versus 15.50 +/- 4.85 pg/mL; thrombomodulin, 2.96 +/- 0.34 versus 2.85 +/- 0.37 ng/mL).

CONCLUSIONS
Endothelin-1 production is increased in the pulmonary circulation of patients with mitral stenosis in response to increased pulmonary artery pressure but is not directly related to increased pulmonary vascular tone in this disorder.
Severe congenital mitral stenosis in infants.
Authors: Moore P , Adatia I , Spevak P J , Keane J F , Perry S B , Castaneda A R , Lock J E 
Published: June 2012

BACKGROUND
Despite current medical and surgical therapy, infants with symptomatic congenital mitral stenosis (CMS) continue to have high rates of morbidity and mortality. Catheter balloon dilation has been successful in relieving symptoms in a few older children with CMS but has not been evaluated in infants.

METHODS AND RESULTS
We reviewed the records of 85 infants with CMS to assess severity of CMS, associated cardiac lesions, echocardiographic morphological appearance of the mitral valve, treatment, and outcome. There were five valve morphologies identified: "typical" hypoplastic mitral valve with symmetric papillary muscles (SYMM, 52%), supravalvar mitral ring (SVMR, 20%), double-orifice mitral valve (DOMV, 11%), hypoplastic mitral valve with asymmetric papillary muscles (ASYMM, 8%), and parachute mitral valve (PARA, 8%). Of the 85 infants, 31 (36%) were severely symptomatic, requiring intervention within the first 2 years. Balloon dilation was performed in 18 infants (age, 8.7 +/- 5.7 months; weight, 5.9 +/- 1.9 kg) and valve surgery in 13 (age, 10.9 +/- 5.9 months; weight, 6.7 +/- 2.1 kg). Balloon dilation decreased the peak transmitral gradient (LAa-LVED) > 30% in 15 of 18 initial attempts, from 20.3 +/- 8.2 to 10.9 +/- 4.9 mm Hg (P < .001), and the mitral valve area increased from 0.7 +/- 0.3 to 1.0 +/- 0.5 cm2/M2 (n = 10, P = .01). No infants died during the initial balloon dilation, although 2 of 3 died during a repeat procedure for restenosis. Other complications included significant mitral regurgitation in 7 of 18 patients (39%), 4 of whom had SVMR. Of the 18 infants, 8 (44%) had persistent symptomatic improvement at a mean follow-up of 14 months (range, 2 to 32 months). The 2-year survival after balloon dilation was 70%; 40% remained free of repeat intervention. Mitral valve surgery in 13 infants consisted of SVMR resections in 7, mitral valve replacements in 4, and LA-to-LV aortic valved homografts in 2. The operative mortality was 30%. Sustained improvement occurred in 8 (6 with SVMR) at 11 to 62 months of follow-up (mean, 30 months), with a 2-year survival of 60%.

CONCLUSIONS
Infants with severe CMS have 2-year mortality rates approaching 40% regardless of treatment modality. Balloon dilation significantly reduces the transmitral gradient in the majority, but symptomatic improvement persists in only 40%. Procedure-related mortality was associated with repeat balloon dilation in patients with left ventricular hypoplasia. Balloon dilation of "typical" CMS can provide symptomatic relief in many infants, allowing postponement of valve replacement, although infants with SVMR do better with surgical management.
Ventricular beats induce variations in cycle length of rapid (type II) atrial flutter in humans. Evidence of leading circle reentry.
Authors: Ravelli F , Disertori M , Cozzi F , Antolini R , Allessie M A 
Published: June 2012

BACKGROUND
Slight variation in cycle lengths of common and rapid atrial flutter in humans is an established phenomenon, but its mechanisms have not been completely clarified. In a previous study, we demonstrated that in common atrial flutter the variations in atrial cycle length were due to atrial stretch affecting the revolution time of a reentrant circuit. In the present study, we investigate the nature of atrial cycle length variations in the rapid type of human atrial flutter.

METHODS AND RESULTS
Atrial interval variations of 17 episodes of rapid atrial flutter in 14 patients were investigated by measuring the sequence of atrial intervals from intraesophageal or intra-atrial leads and the onset of QRS complexes from a surface lead (V1). To study whether interval variation in flutter cycle was related to ventricular activity, a phase plot was constructed in which the flutter cycle length was plotted against the time after the previous QRS complex. This showed that the interval fluctuations were strictly coupled to the moment of ventricular activation. After the onset of the QRS complex, the rapid atrial flutter interval gradually decreased by an average of 4.1% (P < .001) and reached a minimum value after 300 to 600 milliseconds. Thereafter, the intervals increased again until the next ventricular beat occurred. In 10 patients developing both common and rapid atrial flutter, two different phase relations were found. Whereas during common atrial flutter the atrial interval increased after the QRS complex, it decreased during rapid atrial flutter. In three patients, intra-atrial pressure was recorded together with the electrical activity during both common and rapid atrial flutter episodes. This showed that variations in atrial flutter cycle length were associated with the rise of atrial pressure during ventricular contraction.

CONCLUSIONS
These findings indicate a role of contraction-excitation feedback caused by atrial stretch after a ventricular activation. The shortening of the atrial interval after the onset of the QRS complex as found in patients during rapid atrial flutter can be explained by stretch-induced shortening of atrial refractoriness and consequent shortening of the revolution time of a functionally determined intra-atrial circuit.
Effect of calcium channel block on the wall motion abnormality of the idiopathic long QT syndrome.
Authors: De Ferrari G M , Nador F , Beria G , Sala S , Lotto A , Schwartz P J 
Published: June 2012

BACKGROUND
We recently showed the frequent occurrence of an unusual ventricular wall motion abnormality, assessed by echocardiography, in patients with the idiopathic long QT syndrome (LQTS). Two new quantitative indexes were developed: Th1/2 (time needed to reach half of the maximal systolic thickening), which was smaller in LQTS patients than in controls; and TSTh (time spent at a very low thickening rate before rapid relaxation), which was much greater in LQTS patients, indicating the presence of a slow contraction in the late thickening phase. This marked late systolic "plateau," either rectilinear or with a peculiar double peak pattern, was significantly more frequent in patients with a history of syncope or cardiac arrest. The mechanism underlying this puzzling phenomenon remained unexplained.

METHODS AND RESULTS
The present study assessed the effects of the calcium channel blocker verapamil on the contraction pattern in 10 LQTS patients (9 females and 1 male; mean age, 19 +/- 7 years) with a marked plateau pattern and in 6 healthy controls (4 females and 2 males; mean age, 28 +/- 5 years). Either verapamil (0.1 mg/kg) or saline was randomly injected over 2 minutes. Saline had no effect. In LQTS patients, verapamil increased Th1/2 by 27%, from 16.9 +/- 3.2% to 21.4 +/- 3.9% of the cardiac cycle (P = .005), and dramatically reduced TSTh by 92%, from 13.7 +/- 5.3% to 1.08 +/- 0.6% of the cardiac cycle (P < .00001). At the peak effect of verapamil, the contraction pattern of all patients was normal. In healthy control subjects, verapamil did not significantly change either Th1/2 (from 17.6 +/- 2.5% to 18.5 +/- 3.5% of the cardiac cycle) or TSTh (from 0.92 +/- 0.47% to 1.17 +/- 0.74%).

CONCLUSIONS
This study demonstrates that the wall motion abnormality of LQTS is completely abolished by verapamil. These results suggest that symptomatic LQTS patients may have an abnormal increase in the intracellular calcium concentration before relaxation has completed, possibly linked to an early afterdepolarization, and that the contraction abnormality may be the mechanical equivalent of an early afterdepolarization.
Vasodepressor reaction induced by inferior vena cava occlusion and isoproterenol in the rat. Role of beta 1- and beta 2-adrenergic receptors.
Authors: Waxman M B , Asta J A , Cameron D A 
Published: June 2012

BACKGROUND
Testing for the susceptibility of vasodepressor reaction in humans involves the combination of restriction of venous return by passive upright tilting and the administration of isoproterenol. We developed an experimental rat model in which vasodepressor reactions are induced when the inferior vena cava is occluded during an infusion of isoproterenol. The reactions are characterized by the development of paradoxical bradycardia during the period of inferior vena cava occlusion.

METHODS AND RESULTS
Inferior vena cava occlusion was performed for 60 seconds, and the maximal changes in RR interval were measured during seven states as follows: (1) when inferior vena cava occlusion was performed under control conditions in 40 rats, the rate accelerated in all 40 rats (delta RR, -15.6 +/- 1.9 milliseconds in 25 rats, P < .001; delta RR, -13.3 +/- 1.7 milliseconds in 10 rats, P < .001); (2) when inferior vena cava occlusion was performed in 25 rats during an infusion of isoproterenol, a vasodepressor reaction was observed in all rats as the heart rate slowed (delta RR, +92.7 +/- 8.3 milliseconds, P < .001); (3) when inferior vena cava occlusion was performed in 10 rats during an infusion of dobutamine, a selective beta 1-agonist, a vasodepressor reaction was observed in all rats as the heart rate slowed (delta RR, +63.3 +/- 10.6 milliseconds, P < .001); (4) when inferior vena cava occlusion was performed in 5 rats during an infusion of salbutamol, a selective beta 2-agonist, vasodepressor reaction was not observed as the heart rate accelerated in all rats (delta RR, -11.4 +/- 2.8 milliseconds, P < .002); (5) the vasodepressor reaction induced by either dobutamine or isoproterenol was inhibited by atenolol, a selective beta 1-adrenergic receptor antagonist; (6) the vasodepressor reaction induced by isoproterenol was inhibited by propranolol (lipophilic) and sotalol (nonlipophilic) beta-blockers and there was a dose-dependent attenuation by propranolol of the maximal RR interval slowing during inferior vena cava occlusion; and (7) butoxamine, a selective beta 2-adrenergic receptor antagonist, attenuated but did not block the vasodepressor reaction observed during an infusion of isoproterenol.

CONCLUSIONS
Reduced cardiac volume combined with beta 1-adrenergic stimulation can stimulate a vasodepressor reaction in rats. beta 2-Adrenergic receptors play little or no role in the reaction. The vasodepressor reaction can be blocked by selective or nonselective beta 1-adrenergic antagonists independent of the drug's ability to penetrate the central nervous system. The application of these findings to humans remains to be elucidated.
Contraction uncoupling with butanedione monoxime versus low calcium or high potassium solutions on flow and contractile function of isolated hearts after prolonged hypothermic perfusion.
Authors: Stowe D F , Boban M , Graf B M , Kampine J P , Bosnjak Z J 
Published: June 2012

BACKGROUND
Normal ionic perfusate containing butanedione monoxime (BDM), a reversible myofilament inhibitor, could be better than either a high potassium (KCl) or a low calcium (CaCl2) perfusate for long-term cardiac preservation. This hypothesis was tested in 70 isolated guinea pig hearts.

METHODS AND RESULTS
Three groups--time control (8 hours, 37 degrees C), cold control (22 hours, 3.8 degrees C), and cold+BDM (22 hours)--were perfused with typical Krebs-Ringer solution (2.5 mmol/L CaCl2 and 4.5 mmol/L KCl). Two other groups were cold perfused for 22 hours either with 2.5 mmol/L CaCl2 + 20 mmol/L KCl (high) or with 0.5 mmol/L CaCl2 (low) + 4.5 mmol/L KCl. These changes were maintained from 20 minutes before cold perfusion until 30 minutes after rewarming to 37 degrees C. Coronary vasodilator reserve was tested before cold perfusion and 2 hours after warm reperfusion with adenosine (Ade), acetylcholine (Ach, endothelium dependent), and nitroprusside (NP, endothelium independent). Each treatment decreased left ventricular pressure (LVP) by more than 80% before cold perfusion. During warm reperfusion, LVP was lower in cold control (-72 +/- 5%), high KCl (-76 +/- 4%), and low CaCl2 (-80 +/- 4%) groups than in BDM (-38 +/- 3%) or time control (-18 +/- 4%) groups; coronary flow (CF) was lower in high KCl (-67 +/- 4%) and low CaCl2 (-54 +/- 7%) groups than in cold control (-37 +/- 6%), BDM (-30 +/- 5%), or time control (+2 +/- 3%) groups; and percent oxygen extraction (controls, 62 +/- 4%) was higher in the high KCl group (83 +/- 6%) than in cold control (72 +/- 3%), BDM (73 +/- 3%), low CaCl2 (72 +/- 5%), or time control (63 +/- 3%) groups. CF responses to Ade, Ach, and NP (+103 +/- 7%, +24 +/- 5%, and +34 +/- 5% before cold) were attenuated (+76 +/- 6%, +18 +/- 5%, and +23 +/- 4%) in the time control group (5 hours later), were reduced but present in the BDM group (+10 +/- 5%, -5 +/- 5%, and -5 +/- 5%), and were absent in both low CaCl2 and high KCl groups after 2 hours of reperfusion.

CONCLUSIONS
Normal ionic BDM solution better preserves cardiac function and basal CF after prolonged cold perfusion than do cold control, high KCl, and low CaCl2 solutions. Vasodilatory capacity is markedly diminished after perfusion with either the high KCl or the low CaCl2 solution.
Exhaled nitric oxide as a marker for organic nitrate tolerance.
Authors: Husain M , Adrie C , Ichinose F , Kavosi M , Zapol W M 
Published: June 2012

BACKGROUND
This study was designed to demonstrate the development of biochemical tolerance to organic nitrates by measuring levels of exhaled gaseous nitric oxide (NO) in lambs given intravenous (IV) nitroglycerin or sodium nitroprusside.

METHODS AND RESULTS
IV injections of nitroglycerin or sodium nitroprusside produced dose-dependent and sustained increases in the exhaled levels of nitric oxide measured by chemiluminescence in awake lambs with tracheostomies. After a 6-hour IV infusion of 25 micrograms.kg-1.min-1 nitroglycerin, peak exhaled NO levels were significantly reduced (-53.6 +/- 4.9%, mean +/- SEM, P < .001) and systemic hypotensive responses were attenuated (-52.6 +/- 5.9%, P < .001) after an IV challenge of nitroglycerin but not sodium nitroprusside. After a subsequent 12-hour nitroglycerin-free period, there was complete recovery of NO excretion in exhaled breath and a return to baseline of systemic hypotensive changes on administration of IV nitroglycerin boluses. For IV sodium nitroprusside challenges, pulmonary NO excretion and systemic hypotensive responses remained constant throughout the study. Challenges with IV nitroglycerin but not sodium nitroprusside during a 12-hour nitroglycerin-free period resulted in delayed biochemical recovery with various exhaled NO levels and systemic hypotensive responses to challenges with IV nitroglycerin.

CONCLUSIONS
Measurements of exhaled NO provide in vivo, noninvasive evidence for the development of biochemical tolerance to nitroglycerin. There was reduced NO release into exhaled gas from the pulmonary vasculature concomitant with evidence of tolerance to nitroglycerin vasodilation in the systemic circulation.
Peripheral assessment of phenylephrine-induced vasoconstriction by laser Doppler flowmetry and its potential relevance to homeostatic mechanisms.
Authors: Silverman D G , Jotkowitz A B , Freemer M , Gutter V , O'Connor T Z , Braverman I M 
Published: June 2012

BACKGROUND
Cutaneous laser Doppler flowmetry enables monitoring of changes in skin perfusion by quantifying the phase shift of laser light induced by moving red blood cells under a fiberoptic probe. It thus can identify the presence of and response to a vasoconstrictive stimulus. However, aspects of the technique must be defined before it can be used with maximum effectiveness. We evaluated the responses of two different laser Doppler outputs, the concentration of moving blood cells (CMBC) and red cell flux (CMBC times cell velocity), and the responses at two sites of probe application, the finger and forearm, during systemic infusions of phenylephrine.

METHODS AND RESULTS
Eight healthy volunteers were monitored with a brachial blood pressure cuff, ECG, and laser Doppler flowmeter probes applied to the palmar surface of the fourth finger and volar forearm of the arm opposite the pressure cuff. After baseline readings were obtained, the subjects received three 10-minute intravenous infusions of phenylephrine at rates of 0.4, 0.8, and 1.6 micrograms.kg-1.min-1. The two parameters, flux and CMBC, trended similarly. Flux and CMBC at the finger declined significantly in response to each infusion (P < .05 using repeated-measures ANOVA with Duncan's multiple range test). In contrast, flux and CMBC of the forearm had highly variable responses, with an overall increase during each infusion (P < .05 for % delta of forearm versus % delta of finger readings during the 0.4 microgram.kg-1.min-1 infusion). Heart rate declined significantly during each infusion, consistent with a baroreceptor-mediated response, even though systolic and diastolic blood pressures each increased by less than 2 mm Hg during the 0.4 microgram.kg-1.min-1 infusion.

CONCLUSIONS
As expected, laser Doppler readings at the finger decreased during infusion of an alpha 1-agonist. Although, like the digital vessels, forearm vessels have the potential to constrict, the increases in forearm readings suggest that these vessels are highly susceptible to homeostatic responses. The increase in CMBC (a parameter that is sensitive primarily to local changes in vascular caliber) suggested vasodilation of the underlying vessels. The forearm vasodilation and the concomitant decline in heart rate most likely represented vagally mediated baroreceptor activity, which was altered even though blood pressure changed minimally during the 0.4 microgram.kg-1.min-1 infusion. Thus, integrated assessment of skin perfusion at the finger and forearm may provide valuable information about the direct and indirect effects of a vasoactive stimulus. The present application of laser Doppler flowmetry suggests activation of vasodilatory reflexes despite minimal changes in blood pressure.
Insulin inhibits serotonin-induced Ca2+ influx in vascular smooth muscle.
Authors: Kahn A M , Allen J C , Seidel C L , Song T 
Published: June 2012

BACKGROUND
Insulin in physiological concentrations attenuates the agonist-induced intracellular Ca2+ ([Ca2+]i) transient and inhibits contraction in individual nonproliferated cultured canine femoral artery vascular smooth muscle cells (VSMCs). In the present study, we wished to define the effects of insulin on individual components of Ca2+ transport in vascular smooth muscle.

METHODS AND RESULTS
Insulin (40 microU/mL) attenuated the 5-hydroxytryptamine (5-HT, serotonin; 10(-5) mol/L)-induced [Ca2+]i transient (measured by fura 2 fluorescence) in primary confluent canine femoral artery VSMCs in the presence of extracellular Ca2+. In Ca(2+)-free media, the 5-HT-induced [Ca2+]i transient was reduced by 42% and was not affected by insulin. This finding suggested that insulin inhibits 5-HT-induced Ca2+ influx but does not affect sarcolemmal Ca2+ efflux or Ca2+ release from intracellular stores. In support of those conclusions, we found that insulin inhibited the 5-HT-induced component of Mn2+ (a Ca2+ surrogate) influx (measured by fura 2 fluorescence quenching at the Ca2+ isosbestic excitation wavelength). In addition, 5-HT stimulated the rates of 45Ca2+ efflux from intact cells (a measure of sarcolemmal Ca2+ efflux) and from saponin-permeabilized cells (a measure of Ca2+ release from intracellular stores), but insulin did not affect these rates of 45Ca2+ efflux.

CONCLUSIONS
We conclude that a physiological insulin concentration attenuates the 5-HT-induced [Ca2+]i transient in confluent primary cultured canine femoral artery VSMCs by inhibiting the 5-HT-induced component of Ca2+ influx but not by affecting sarcolemmal Ca2+ efflux or Ca2+ release from intracellular stores.
Scar remodeling and transmural deformation after infarction in the pig.
Authors: Holmes J W , Yamashita H , Waldman L K , Covell J W 
Published: June 2012

BACKGROUND
Changes in stress and tissue material properties have been proposed as important mechanical factors that may influence infarct expansion and subsequent healing. Because such changes will be reflected by alterations in the finite deformation of the tissue, we examined the direction and magnitude of myocardial deformation after coronary ligation in the pig.

METHODS AND RESULTS
Gold beads were implanted in the left ventricular free wall of five pigs. After ligation of the coronary supply to the region containing the markers, we used biplane cineradiography to reconstruct the three-dimensional deformations of the myocardium during single cardiac cycles as well as the remodeling deformations that occurred over time. Deformations were studied at 1 and 3 weeks after infarction. The analysis of single cardiac cycles revealed permanent loss of systolic shortening immediately after ligation. However, significant passive systolic wall thickening (P < .001) and large shears were observed at 3 weeks in regions composed almost entirely of collagen. The analysis of remodeling deformations at 1 week revealed infarct expansion with a predominant axis that varied widely. At 3 weeks, a 30% to 60% reduction in local tissue volume was measured in the infarct region, with the principal direction of scar shrinkage nearly circumferential in all animals (range, -2 degrees to 35 degrees).

CONCLUSIONS
We conclude that infarct expansion and scar shrinkage may be controlled by different factors. In addition, we conclude that measurement of systolic wall thickening alone is not always adequate to assess postinfarction regional contractile function.