bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glibenclamide antagonizes adenosine A1 receptor-mediated cardioprotection in stunned canine myocardium.
Authors: Yao Z , Gross G J 
Published: June 2012

BACKGROUND
The main objective of the present study was to determine the role of adenosine in the development of myocardial stunning following multiple, brief periods of coronary artery occlusion as well as the subtype of adenosine receptor (A1 or A2) involved. A second objective was to determine if there was an interaction between the adenosine A1 receptor and the ATP-dependent K channel (KATP).

METHODS AND RESULTS
The effects of the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and agonist cyclopentyladenosine (CPA), the selective A2 receptor agonist CGS 21680, and the KATP channel blocker glibenclamide on myocardial stunning produced by repetitive coronary artery occlusions were studied in barbital-anesthetized dogs. Regional segment function was measured with sonomicrometry. Under control conditions, six 5-minute periods of coronary occlusion interspersed with 10-minute periods of reperfusion and ultimately followed by 2 hours of reperfusion produced regional segment dysfunction. Pretreatment with intravenous infusion of CPA (2.0 micrograms.kg-1.min-1) improved percent segment shortening throughout reperfusion, whereas pretreatment with DPCPX (1.0 mg/kg i.v. bolus) significantly worsened the recovery of postischemic contractile function. In contrast, neither DPCPX nor CPA had any effect on the recovery of contractile function when administered before the second coronary occlusion. Furthermore, pretreatment with CGS 21680 (0.2 micrograms.kg-1.min-1) did not affect the recovery of percent segment shortening. In addition, pretreatment with a low dose of glibenclamide (0.1 mg/kg) had no effect on percent segment shortening by itself but completely abolished the beneficial effect of CPA. Importantly, the effects of the various agents on percent segment shortening were independent of difference in systemic hemodynamics, collateral blood flow, or ischemic bed size.

CONCLUSIONS
These results suggest that stimulation of myocardial adenosine A1 receptors, particularly when induced by the initial coronary artery occlusion, is cardioprotective during repetitive, brief periods of coronary artery occlusion and that these beneficial actions may be partially mediated via a glibenclamide-sensitive mechanism, possibly opening of myocardial KATP channels.
Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans.
Authors: Lefroy D C , Crake T , Uren N G , Davies G J , Maseri A 
Published: June 2012

BACKGROUND
NG-Monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis, was used to determine the effects of inhibition of nitric oxide synthesis in the human coronary circulation.

METHODS AND RESULTS
Twelve patients (mean age, 52 +/- 2 years) with normal epicardial coronary arteries were studied. The surface ECG, systemic blood pressure, and coronary venous oxygen saturation (coronary SvO2), an index of coronary blood flow, were monitored continuously. Coronary artery diameter was measured by quantitative arteriography. L-NMMA was given as intracoronary infusions at 2 mL/min via the diagnostic arteriography catheter. In two patients, low doses (0.01 to 5 mumol/min) of L-NMMA were infused into the nondominant right coronary artery. There was no evidence of ischemia in these patients, who were not included in the final analysis. In 10 patients, higher doses of L-NMMA (4, 10, and 25 mumol/min, each for 5 minutes) were infused into the left coronary artery. In six patients, incremental doses of acetylcholine were infused (1, 10, and 100 nmol/min, each for 3 minutes) before and after the L-NMMA infusion. Finally, in all patients, sodium nitroprusside, a nitric oxide donor, was infused. No patient developed myocardial ischemia. The heart rate and systemic blood pressure remained unchanged throughout the infusions. L-NMMA (25 mumol/min), compared with the control saline infusion, caused a significant reduction in distal (-5.9 +/- 2.1%, P = 0.021) but not proximal left anterior descending coronary artery (LAD) diameter and a fall in coronary SvO2 from 37.5 +/- 2.8% to 34.3 +/- 2.8% (P = 0.019). Sodium nitroprusside dilated the proximal (17.8 +/- 6.9%, P = 0.033) and distal (24.5 +/- 6.5%, P = 0.006) LAD and increased the coronary SvO2 to 61.6 +/- 5.0% (P = 0.0002). Acetylcholine caused significant dilatation of the distal (13.8 +/- 5.4%, P = 0.049) but not proximal LAD and a significant increase in coronary SvO2 from 36.5 +/- 3.5% to 59.2 +/- 2.8% (P < 0.0001). After L-NMMA, acetylcholine-induced dilatation of the distal LAD was abolished, but the rise in coronary SvO2 was unchanged.

CONCLUSIONS
Inhibition of nitric oxide synthesis in the human coronary circulation caused a decrease in basal distal LAD diameter and basal coronary blood flow assessed by coronary SvO2, indicating that there is a small basal release of nitric oxide in the distal epicardial coronary arteries and resistive vessels. Distal epicardial coronary artery dilatation in response to acetylcholine is nitric oxide dependent, but coronary resistive vessel dilatation is not.
Ventricular expression of brain natriuretic peptide in hypertrophic cardiomyopathy.
Authors: Hasegawa K , Fujiwara H , Doyama K , Miyamae M , Fujiwara T , Suga S , Mukoyama M , Nakao K , Imura H , Sasayama S 
Published: June 2012

BACKGROUND
Brain natriuretic peptide (BNP), as a cardiac hormone, is expressed together with atrial natriuretic peptide (ANP) in the ventricles in congestive heart failure. However, the ventricular expression of BNP in hypertrophic cardiomyopathy (HCM) with normal systolic function is still unclear.

METHODS AND RESULTS
The study population consisted of 39 HCM patients with asymmetric septal hypertrophy and 10 control subjects without any specific cardiac disease. Eleven cases of HCM were obstructive (HOCM), and the other 28 cases were nonobstructive (HNCM). All of these patients had a normal ejection fraction. Immunohistochemical analysis of endomyocardial biopsy specimens with specific monoclonal antibodies showed BNP immunoreactivity in the HOCM group (5/10, 50%) but not in the HNCM group (0/22) or in control subjects (0/5). In HOCM, left ventricular end-diastolic pressure was significantly higher in the BNP-positive patients than the BNP-negative patients. Histological changes such as myocardial fiber disarray, hypertrophy of myocytes, and fibrosis were greater in BNP-positive patients than BNP-negative patients in HCM. However, the expression had no significant relation with other clinical parameters. The elevation of the BNP plasma level versus control subjects was marked in both HOCM (85-fold) and HNCM (23-fold). By contrast, the elevation of the ANP plasma level versus control subjects was mild in HOCM (5.7-fold) and HNCM (4.2-fold). The ratio of BNP level to ANP level was higher in HOCM (4.16) than in HNCM (1.46) and control subjects (0.28), and it was higher than the ratio previously reported for severe congestive heart failure (1.72).

CONCLUSIONS
These findings suggest that BNP is expressed in the ventricular myocytes of HCM with normal systolic function. In HOCM, ventricular expression of BNP may be augmented in response to both obstruction and diastolic dysfunction.
Dobutamine stress echocardiography identifies hibernating myocardium and predicts recovery of left ventricular function after coronary revascularization.
Authors: Cigarroa C G , deFilippi C R , Brickner M E , Alvarez L G , Wait M A , Grayburn P A 
Published: June 2012

BACKGROUND
The identification of hibernating myocardium is important in selecting patients who will benefit from coronary revascularization. This study was performed to determine whether dobutamine stress echocardiography (DSE) could identify hibernating myocardium and predict improvement in regional systolic wall thickening after revascularization.

METHODS AND RESULTS
DSE was performed in 49 consecutive patients with multivessel coronary disease and depressed left ventricular function. Contractile reverse during DSE was defined by the presence of two criteria: (1) improved systolic wall thickening in at least two adjacent abnormal segments and (2) > or = 20% improvement in regional wall thickening score. Postoperative echocardiograms were evaluated for improved regional wall thickening in 25 patients at least 4 weeks after successful coronary revascularization. All studies were read in blinded fashion. Contractile reserve during DSE was present in 24 (49%) of 49 patients. The presence or absence of contractile reserve on preoperative DSE predicted recovery of ventricular function in the 25 patients who underwent successful revascularization. Thus, 9 of 11 patients with contractile reserve had improved systolic wall thickening after revascularization (hibernating myocardium), whereas 12 of 14 patients without contractile reserve did not improve (P = .003).

CONCLUSIONS
Dobutamine stress echocardiography provides a simple, cost-effective, and widely available method of identifying hibernating myocardium and predicting improvement in regional left ventricular wall thickening after coronary revascularization. This technique may be clinically valuable in the selection of patients for coronary revascularization.
Monoclonal antibody to L-selectin attenuates neutrophil accumulation and protects ischemic reperfused cat myocardium.
Authors: Ma X L , Weyrich A S , Lefer D J , Buerke M , Albertine K H , Kishimoto T K , Lefer A M 
Published: June 2012

BACKGROUND
Interaction of CD11/CD18 located on neutrophil membranes with its endothelial counter-receptor, intercellular adhesion molecule-1, plays a major role in polymorphonuclear leukocyte (PMN)-mediated endothelial dysfunction and myocardial injury associated with ischemia and reperfusion. However, PMN-derived L-selectin, which is thought to play an early role in PMN rolling along the vascular endothelium, has not been studied in a setting of myocardial ischemia and reperfusion.

METHODS AND RESULTS
In this study, we evaluated the effects of a monoclonal antibody against L-selectin, DREG-200, in a feline model of myocardial ischemia (1.5 hours) and reperfusion (4.5 hours). DREG-200 (1 mg/kg) or an isotype-matched IgG1 antibody, MAb R3.1, which does not cross-react in cats, was administered as a bolus 10 minutes before reperfusion. In MAb R3.1-treated cats, myocardial ischemia followed by reperfusion resulted in significant coronary vascular endothelial dysfunction, elevated cardiac myeloperoxidase activity indicative of neutrophil accumulation in the ischemic myocardium, and severe myocardial injury. In contrast, administration of DREG-200 at 1 mg/kg significantly attenuated myocardial necrosis (14 +/- 4 versus 32 +/- 3 expressed as percentage of area at risk, P < .001) and attenuated coronary endothelial dysfunction (P < .01) associated with ischemia/reperfusion. Moreover, myeloperoxidase activity in the ischemic myocardium was significantly lower than MAb R3.1-treated cats (0.4 +/- 0.1 versus 0.9 +/- 0.2 U/100 mg tissue, P < .05).

CONCLUSIONS
These results demonstrate that blocking L-selectin with DREG-200 exerts a significant cardioprotective effect in a feline model of myocardial ischemia and reperfusion, indicating that L-selectin plays a significant role in mediating PMN accumulation and PMN-induced endothelial and myocardial injury after ischemia and reperfusion.
Electrocardiographic correlates of spontaneous termination of ventricular tachycardia in patients with coronary artery disease.
Authors: Duff H J , Mitchell L B , Gillis A M , Sheldon R S , Chudleigh L , Cassidy P , Chiamvimonvat N , Wyse D G 
Published: June 2012

BACKGROUND
In vitro studies have reported that beat-to-beat variance in tachycardia cycle length and in conduction and repolarization properties can result in spontaneous termination of reentrant arrhythmias. The purpose of this study was to define the ECG patterns associated with spontaneous termination of ventricular tachycardia in humans late after myocardial infarction.

METHODS AND RESULTS
The QRS durations, QT intervals, and cycle lengths were measured on a beat-to-beat basis during episodes of sustained and spontaneously terminating ventricular tachycardias (VT) induced at antiarrhythmic drug-free and drug-assessment electrophysiological studies. Twenty-six patients were studied. Four categories of inducible ventricular tachycardia were studied: inducible sustained ventricular tachycardia in an antiarrhythmic drug-free state, spontaneously terminating ventricular tachycardia in an antiarrhythmic drug-free state, sustained ventricular tachycardia on antiarrhythmic therapy, and spontaneously terminating ventricular tachycardia on antiarrhythmic therapy. The ECG patterns that were statistically related to spontaneous termination of ventricular tachycardia included impingement of the QTP interval on the tachycardia cycle length (P < .001) both in the presence and absence of drugs, transient shortening of QRS just before termination, and paradoxical prolongation of QTP after abrupt shortening of ventricular tachycardia cycle length. In addition, greater beat-to-beat variances in tachycardia cycle lengths, QT intervals, and QRS durations were statistically associated with spontaneously terminating ventricular tachycardia. These ECG patterns did not occur during sustained episodes of ventricular tachycardia during the antiarrhythmic drug-free state or during ineffective antiarrhythmic drug therapy.

CONCLUSIONS
A dynamic interplay between QRS duration, QT interval, and cycle length of tachycardia and their variances are associated with spontaneous termination of ventricular tachycardia in humans late after infarction. This study of ECG changes associated with spontaneous termination of ventricular tachycardia provides insight into potential mechanisms of antiarrhythmic drug efficacy.
Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation.
Authors: Kaye D , Thompson J , Jennings G , Esler M 
Published: June 2012

BACKGROUND
Hypertension frequently complicates the use of cyclosporine A (CyA) therapy, and it has been suggested that sympathoexcitation may be the underlying mechanism in this form of hypertension.

METHODS AND RESULTS
To further investigate the possibility of a neurogenic mechanism for this hypertensive effect, we studied the effects of CyA on renal blood flow (n = 11), forearm blood flow (n = 8), and sympathetic nervous system activity, assessed by renal and whole-body radiolabeled norepinephrine plasma kinetics and muscle sympathetic nerve firing (using microneurography) in cardiac transplant recipients receiving CyA and a reference group of healthy age-matched control subjects (n = 17). In 11 cardiac transplant patients (2 hours after cyclosporine dose), renal blood flow was significantly lower than that in 8 control subjects (680 +/- 88 vs 1285 +/- 58 mL/min, P < .001). In 5 of these transplant patients, renal blood flow was measured before and for 2 hours after oral cyclosporine and fell progressively over this period, by 37% (P < .01). Total body and renal norepinephrine spillover rates in transplant patients were similar to those in control subjects (3070 +/- 538 vs 2618 +/- 313 pmol/min and 579 +/- 124 vs 573 +/- 95 pmol/min, respectively), and there was no progressive effect in the 2 hours after cyclosporine dosing. Forearm blood flow was increased 2 hours after CyA administration (1.74 +/- 0.31 to 3.12 +/- 0.50 mL x 100 mL-1 x min-1, P < .001), whereas mean arterial blood pressure and noninvasively determined cardiac output (indirect Fick method) were unchanged. Muscle sympathetic nerve discharge rates recorded in 6 of these transplant patients were not different from those in 9 healthy control subjects (37.9 +/- 10.1 vs 41.3 +/- 2.3 bursts per 100 beats per minute). During 90 to 120 minutes of recording after cyclosporine dosing, nerve firing rates remained unchanged.

CONCLUSIONS
CyA therapy causes acute renal vasoconstriction without accompanying systemic hemodynamic effects. These renal effects are nonneural, not being attributable to sympathoexcitation.
Functional and neurochemical evidence for partial cardiac sympathetic reinnervation after cardiac transplantation in humans.
Authors: Kaye D M , Esler M , Kingwell B , McPherson G , Esmore D , Jennings G 
Published: June 2012

BACKGROUND
The presence of cardiac reinnervation in humans after cardiac transplantation has been widely debated, based on the application of differing methods for the assessment of neuronal function. Some of these techniques have been rather indirect; consequently, the time course and extent of cardiac reinnervation remains uncertain.

METHODS AND RESULTS
To test for the presence of cardiac reinnervation after transplantation, we examined neurochemical (radiolabeled norepinephrine [NE] kinetics) and functional markers (power spectral analysis, heart rate response to exercise) of cardiac sympathetic nerve integrity in 15 cardiac transplantation recipients and 25 healthy control subjects of similar age. Cardiac transplantation subjects were studied 9 weeks to 8 years after cardiac transplantation (10 "early" patients < 18 months and 5 "late" patients > 2 years after cardiac transplantation). At rest, cardiac NE spillover was markedly attenuated early after transplantation (11.2 +/- 18.3 pmol/min) compared with subjects late after transplantation (105 +/- 11 pmol/min, P < .01) or in healthy control subjects (103 +/- 15 pmol/min, P < .01). Heart rate variability (measured by total spectral power) was significantly reduced in cardiac transplantation recipients compared with control subjects (59.4 +/- 30 vs 1673 +/- 516 milliseconds squared; P < .05), with evidence of a trend toward increasing spectral power late after transplantation. During exercise, the cardiac NE spillover was significantly lower in early cardiac transplantation recipients when compared with control subjects (163 +/- 50 vs 1876 +/- 418 pmol/min, P < .01). Late cardiac transplantation subjects showed a response intermediate (1080 +/- 254 pmol/min) between that of the early cardiac transplantation and control groups. However, measurements of the neuronal reuptake process for NE (assessed by the fractional extraction of plasma labeled NE across the heart and tritiated dihydroxyphenylglycol release) were significantly depressed in both early and late cardiac transplantation subjects.

CONCLUSIONS
The present study demonstrates a partial restoration of cardiac sympathetic nerve function in humans up to 8 years after heart transplantation.
Calcium antagonists differently inhibit proliferation of human coronary smooth muscle cells in response to pulsatile stretch and platelet-derived growth factor.
Authors: Yang Z , Noll G , Lüscher T F 
Published: June 2012

BACKGROUND
Vascular smooth muscle cell proliferation is the key event of coronary artery disease. Mechanical forces, in particular, pulsatile stretch and platelet-derived growth factor, may play an important role.

METHODS AND RESULTS
Vascular smooth muscle cells were cultured from the media of human left descending coronary arteries obtained from organ donors using the explant method. To study effects of pulsatile stretch on vascular smooth muscle cell proliferation, a computer-controlled in vitro pulsatile stretch device was used. Cells were seeded onto Flex I culture plates with deformable membranes and exposed to pulsatile stretch (60 cycles per minute) and/or growth factors. Proliferation of smooth muscle cells was determined by 3H-thymidine incorporation. Pulsatile stretch markedly stimulated 3H-thymidine incorporation of coronary smooth muscle cells (180 +/- 15 to 432 +/- 27 cpm/10(5) cells; P < .05) after 24 hours and increased cell number after 6 days (10.3 +/- 0.7 x 10(4)/mL; P < .05). Platelet-derived growth factor-AB (0.01 to 10 ng/mL) concentration-dependently stimulated 3H-thymidine incorporation in coronary smooth muscle cells (EC50, 0.1 ng/mL) and had additive effects with pulsatile stretch. The Ca2+ antagonist verapamil (10(-7) to 10(-5) M) concentration-dependently inhibited proliferation stimulated by platelet-derived growth factor back to control levels (P < .05 to .01) but not that induced by pulsatile stretch.

CONCLUSIONS
Pulsatile stretch and platelet-derived growth factor are potent stimuli for proliferation of coronary smooth muscle cells. The selective inhibitory effect of a Ca2+ antagonist on smooth muscle cell proliferation stimulated by platelet-derived growth factor but not by pulsatile stretch may explain why the drugs have only modest antiatherogenic effects in patients with coronary artery disease.
The ability of several short-term measures of RR variability to predict mortality after myocardial infarction.
Authors: Bigger J T , Fleiss J L , Rolnitzky L M , Steinman R C 
Published: June 2012

BACKGROUND
We studied 715 patients 2 weeks after myocardial infarction to test the hypothesis that short-term power spectral measures of RR variability (calculated from 2 to 15 minutes of normal RR interval data) will predict all-cause mortality or arrhythmic death.

METHODS AND RESULTS
We performed power spectral analyses on the entire 24-hour RR interval time series. To compare with the 24-hour analyses, we selected short segments of ECG recordings from two time periods for analysis: 8 AM to 4 PM and midnight to 5 AM. The former corresponds to the time interval during which short-term measures of RR variability would most likely be obtained. The latter, during sleep, represent a period of increased vagal tone, which may simulate the conditions that exist when patients have a signal-averaged ECG recorded, ie, lying quietly in the laboratory. Four frequency domain measures were calculated from spectral analysis of heart period data over a 24-hour interval. We computed the 24-hour power spectral density and calculated the power within three frequency bands: (1) 0.0033 to < 0.04 Hz, very low frequency power, (2) 0.04 to < 0.15 Hz, low frequency power, and (3) 0.15 to 0.40 Hz, high frequency power. In addition, we calculated the ratio of low to high frequency power. These measures were calculated for 15-, 10-, 5-, and 2-minute segments during the day and at night. Mean power spectral values from short periods during the day and night were similar to 24-hour values, and the correlations between short segment values and 24-hour values were strong (many correlations were > or = 0.75). Using the optimal cutpoints determined previously for the 24-hour power spectral values, we compared the survival experience of patients with low values for RR variability in short segments of ECG recordings to those with high values. We found that power spectral measures of RR variability were excellent predictors of all-cause, cardiac, and arrhythmic mortality and sudden death. Patients with low values were 2 to 4 times as likely to die over an average follow-up of 31 months as were patients with high values. The power spectral measures of RR variability did not predict arrhythmic or sudden deaths substantially better than all-cause mortality.

CONCLUSIONS
Power spectral measures of RR variability calculated from short (2 to 15 minutes) ECG recordings are remarkably similar to those calculated over 24 hours. The power spectral measures of RR variability are excellent predictors of all-cause mortality and sudden cardiac death.