bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of cardiac sympathetic afferents during coronary occlusion. Evidence for reflex activation of sympathetic nervous system during transmural myocardial ischemia in the dog.
Authors: Minisi A J , Thames M D 
Published: June 2012

BACKGROUND
Left ventricular sympathetic afferent nerves are located mainly in superficial epicardial layers. Reflex excitatory responses mediated by sympathetic afferent nerves have been observed during myocardial ischemia in cats and humans but not in dogs. Previous canine studies have induced ischemia by occlusion of a coronary artery. Extensive collateral circulation in the canine heart may limit ischemia of epicardial layers during simple coronary occlusion, resulting in little stimulation of sympathetic afferent nerves and minimal reflex excitatory responses.

METHODS AND RESULTS
In anesthetized dogs with sinoaortic and vagal deafferentation, we determined whether reflex sympathoexcitatory responses mediated by sympathetic afferents occurred during transmural myocardial ischemia. Reflex sympathoexcitation was quantitated by direct recording from either efferent renal (n = 20) or cardiac (n = 5) sympathetic nerves. Responses of arterial pressure and efferent sympathetic nerve activity were measured during simple occlusion of the anterior descending artery (LAD alone) and during LAD occlusion with a circumflex stenosis (LAD + CIRC). This circumflex stenosis was adjusted to abolish coronary vasodilator reserve without reducing basal flow. We observed significantly greater reflex increases in renal (32 +/- 5%) and cardiac (58 +/- 15%) nerve activity during LAD + CIRC than during LAD alone (14 +/- 6% and 8 +/- 7%, respectively). Reflex changes in renal nerve activity during LAD + CIRC were abolished by interruption of cardiac sympathetic afferent pathways (n = 5). In eight experiments, myocardial blood flow was measured during the two coronary occlusions. These experiments confirmed that LAD + CIRC elicited more transmural ischemia in the LAD distribution than did LAD alone. However, these experiments also revealed that LAD + CIRC elicited endocardial ischemia in the circumflex distribution. In five additional experiments, regional sympathetic deafferentation of the posterior left ventricle by epicardial application of 88% phenol along the atrioventricular groove had no significant effect on renal nerve responses to LAD + CIRC (36 +/- 5% increase before phenol versus 31 +/- 3% increase after phenol). These results indicate that endocardial ischemia in the circumflex distribution did not contribute to the reflex increases in nerve activity that were noted during LAD + CIRC.

CONCLUSIONS
Reflex sympathoexcitation mediated by cardiac sympathetic afferents can be elicited in dogs. However, these responses are significant only during ischemia that is transmural and involves the superficial epicardial layers of the left ventricle.
Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action.
Authors: Kooner J S , Birch R , Frankel H L , Peart W S , Mathias C J 
Published: June 2012

BACKGROUND
Clonidine, a partial presynaptic and postsynaptic alpha-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated.

METHODS AND RESULTS
The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic alpha 2-adrenoceptors.

CONCLUSIONS
Therefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension.
Abnormal hormonal and renal responses to saline load in hypertensive patients with parental history of cardiovascular accidents.
Authors: Volpe M , Lembo G , De Luca N , Lamenza F , Tritto C , Ricciardelli B , Molaro M , De Campora P , Condorelli G , Rendina V 
Published: June 2012

BACKGROUND
Acute cardiac and cerebrovascular accidents are more frequent in hypertensive subjects with a family history of acute vascular accidents. The mechanisms underlying the susceptibility to vascular disease in these subjects are unknown. We investigated whether a parental history of premature heart attack or stroke in hypertensive subjects is associated with abnormalities of sodium handling.

METHODS AND RESULTS
Patients with mild, uncomplicated essential hypertension were divided into two subgroups according to family history: a subgroup with a parental history of premature heart attack or stroke (FV+, n = 18) and a subgroup with a family history completely negative for vascular accidents (FV-, n = 14). The two subgroups were comparable with respect to age, weight, sex distribution, blood pressure, duration of hypertension, cardiovascular risk factors, renal function, and organ damage. Baseline plasma renin activity (PRA), concentrations of aldosterone (PA), atrial natriuretic factor (ANF), and norepinephrine, and urinary electrolyte excretion were also comparable in the two subgroups. Despite these similarities, the responses to an acute saline load, measured under controlled metabolic and experimental conditions, were different in the two subgroups. In the FV+ subgroup at 60 minutes of saline load, PRA fell by 1.0 +/- 0.2 ng/ml/hr and PA concentration by 89.4 +/- 26 pg/ml and ANF concentration increased by 38 +/- 9 pg/ml, whereas in the FV- subgroup the corresponding responses were -2.3 +/- 0.3 ng/ml/hr (p less than 0.005), -190 +/- 43 pg/ml (p less than 0.05), and 80 +/- 13 pg/ml (p less than 0.005), respectively. Urinary sodium excretion was delayed in the FV+ subgroup (270 +/- 67 mu eq/min at 60 minutes) compared with the FV- subgroup (555 +/- 157 mu eq/min at 60 minutes, p less than 0.05). At 120 minutes of saline load, significant (p less than 0.005) differences in PRA and ANF concentration were still observed. In a control group of eight normal subjects the responses to a saline load were comparable to those in the FV- subgroup but greater than those in the FV+ subgroup at 60 minutes.

CONCLUSIONS
These results provide evidence that the hormonal and renal adjustments to an acute salt load are impaired in hypertensive patients with a parental history of vascular accidents. We speculate that abnormalities of sodium handling may represent markers of a more rapid development of vascular injury in human hypertension.
Clinical characteristics of nonfatal myocardial infarction among individuals on prophylactic low-dose aspirin therapy.
Authors: Ridker P M , Manson J E , Buring J E , Goldhaber S Z , Hennekens C H 
Published: June 2012

BACKGROUND
The influence of prophylactic low-dose aspirin on the clinical characteristics of subsequent nonfatal myocardial infarction was examined in the Physicians' Health Study, a randomized, double-blind placebo-controlled trial of alternate-day aspirin (325 mg) among 22,071 US male physicians.

METHODS AND RESULTS
During 60.2 months of follow-up, 342 incident cases of nonfatal myocardial infarction were confirmed (95.2% of all reports): 129 on aspirin and 213 on placebo (p less than 0.00001). Despite this statistically extreme reduction in occurrence of a first nonfatal infarction attributable to aspirin, there were no significant differences in the size, location, electrocardiographic features, or postinfarction left ventricular ejection fraction between the aspirin and placebo groups. Furthermore, among those undergoing angiography, there were no differences in the distribution or number of coronary vessels obstructed.

CONCLUSIONS
These data indicate that chronic platelet inhibition with alternate-day aspirin therapy reduces the risk of a first myocardial infarction but does not appear to have a significant effect on the clinical characteristics of events that are survived. This finding may result from a direct effect of aspirin or from an aspirin-induced shift in infarction severity. Regardless of mechanism, these clinical observations suggest that treatment decisions for acute infarction patients should be made independently of a history of aspirin use.
Differences in the effect of metabolic inhibition on action potentials and calcium currents in endocardial and epicardial cells.
Authors: Kimura S , Bassett A L , Furukawa T , Furukawa N , Myerburg R J 
Published: June 2012

BACKGROUND
Ischemia-induced electrophysiological changes are more prominent in epicardial cells than in endocardial cells. Epicardial action potentials shorten more than endocardial action potentials during ischemia. Since the L-type Ca2+ current plays an important role in the maintenance of action potential duration, we hypothesized that the Ca2+ current is affected more in epicardial cells than in endocardial cells during ischemia.

METHODS AND RESULTS
To test this hypothesis, we examined the effect of metabolic inhibition, a major component of ischemia, on action potentials and the Ca2+ current in single cells isolated from the endocardial and epicardial layers of the feline left ventricle. The membrane voltage and current were measured by using the whole-cell mode of the patch-clamp technique. During control periods, action potentials recorded from epicardial myocytes had lower amplitude, a prominent notch between phases 1 and 2, and shorter action potential duration compared with those recorded from endocardial myocytes. However, the amplitude and current-voltage relation of the Ca2+ current were similar in endocardial and epicardial cells at test potentials of -30 to 60 mV elicited from a holding potential of -40 mV. The time course of inactivation of the Ca2+ current also was identical in the two cell types. After 15 minutes of superfusion with glucose-free Tyrode's solution containing 1 mM CN-, action potential duration was reduced by 13 +/- 7% in endocardial cells and by 80 +/- 9% in epicardial cells (p less than 0.01). The peak Ca2+ current was reduced by 21 +/- 9% in endocardial cells and by 37 +/- 6% in epicardial cells (p less than 0.01).

CONCLUSIONS
We conclude that enhanced depression of the Ca2+ current may account in part for the greater action potential shortening in epicardial cells during ischemia and metabolic inhibition.
Optimal right ventricular filling pressures and the role of pericardial constraint in right ventricular infarction in dogs.
Authors: Calvin J E 
Published: June 2012

BACKGROUND
Previous studies have reported an important role for right ventricular function in the pathophysiology of the low cardiac output state that can accompany right ventricular infarction. Some studies have suggested that right ventricular distensibility impairs right ventricular filling and stroke output; others have demonstrated that the pericardium can mediate depressed left ventricular filling and stroke output.

METHODS AND RESULTS
To determine the role of pericardial constraint and optimal volume loading in an experimental model of right ventricular wall infarction, six mongrel dogs were studied before and after right ventricular wall infarction and after volume loading. The pericardium was then opened in two phases. In the first phase, the pericardium was opened partially to allow the atria to distend freely, and in the second phase, the pericardium was opened completely. The animals were preinstrumented with two sets of piezoelectric crystals attached to the right ventricular free wall, one in the infarct and the other in the noninfarct territory. Left ventricular size was estimated by left ventricular crystals on the anterior wall of the left ventricle. Right ventricular and left ventricular Millar catheters were used to assess intracavitary pressure, and a flat balloon was used to assess intrapericardial pressure. Right ventricular infarction reduced cardiac output by 23% and stroke volume by 30%. End-diastolic segment length and transmural pressure of the left ventricle decreased. Volume loading restored cardiac output to baseline values and was mediated by a significant increase in end-diastolic length in the noninfarct territory. This was achieved by increasing right ventricular end-diastolic pressure from 9 +/- 2 to 16 +/- 3 mm Hg (p less than 0.01). Partial opening of the pericardium mediated significant increases in both end-diastolic segment lengths of the left ventricle and the noninfarct territory. Left ventricular end-diastolic pressure decreased slightly by 3 mm Hg (p = NS). Complete opening of the pericardium increased cardiac output and stroke volume and mediated a significant decrease in right and left ventricular end-diastolic pressures. Left ventricular transmural pressure and end-diastolic segment lengths of the left ventricle and the noninfarct territory increased. Left ventricular diastolic pressure-segment length relations were shifted upward by right ventricular infarction. A partial opening of the pericardium shifted this relation downward in all animals, and complete opening of the pericardium shifted the relation rightward and further downward.

CONCLUSIONS
Cardiac output is restored to baseline values by volume loading sufficient to increase the right ventricular diastolic pressure to 16 +/- 3 mm Hg. Evidence of pericardial constraint was observed and appears to be mediated by an atrioventricular interaction in addition to the direct ventricular interaction.
Detection and localization of prolonged epicardial electrograms with 64-lead body surface signal-averaged electrocardiography.
Authors: Freedman R A , Fuller M S , Greenberg G M , Ershler P R , Lux R L , McLaughlin T B , Menlove R , Green L S , Moddrelle D , Krall R 
Published: June 2012

BACKGROUND
Prolonged, fractionated ventricular electrograms often are detectable after myocardial infarction and are a marker for an arrhythmia-prone state. QRS late potentials detected on the body surface with signal-averaged electrocardiography (SAECG) are thought to arise from the diseased tissue that generates prolonged ventricular electrograms and as such are also a marker for arrhythmias. A limitation of the current SAECG technique is that recordings are obtained from only three bipolar lead pairs. Because late potentials probably arise from multiple small sources in the heart, more extensive sampling of the body surface may contribute additional information to the SAECG: The present study investigates the additional sensitivity of SAECG using 64 body surface leads in detecting prolonged epicardial electrograms and examines its use in determining the epicardial location of prolonged electrograms.

METHODS AND RESULTS
Dogs were studied before and 5-10 days after either lateral left ventricular (n = 13) or right ventricular (n = 8) myocardial infarction. Greater prolongation of signal-averaged QRS duration was detected with 64-lead SAECG (postinfarction QRS duration, 100.3 +/- 16.3 msec) than with three-lead SAECG (postinfarction QRS duration, 89.4 +/- 10.1, p = 0.0005). Nineteen of the 21 dogs (90%) had prolonged epicardial electrograms detected over the infarct. The correlation between epicardial electrogram duration and signal-averaged QRS duration calculated from individual leads was much better for 64-lead SAECG (r = 0.88, p less than 0.0001) than for three-lead SAECG (r = 0.53, p = 0.01), and the difference was most marked in cases with longer electrogram durations (more than 100 msec). Local late potential maxima on the thorax after lateral left ventricular infarction were located to the left and inferior compared with those after right ventricular infarction (p = 0.006).

CONCLUSIONS
SAECG with more extensive recording from the body surface using 64 leads detects greater QRS prolongation than three-lead SAECG, and the longer QRS durations detected correspond to the duration of prolonged epicardial electrograms. Body surface location of late potentials corresponds to the epicardial location of the prolonged electrograms. This application of body surface mapping techniques to SAECG may permit more sensitive detection of arrhythmia-prone states and may aid in identifying arrhythmia sources.
Arterial hemodynamics in human hypertension. Effects of adrenergic blockade.
Authors: Ting C T , Chou C Y , Chang M S , Wang S P , Chiang B N , Yin F C 
Published: June 2012

BACKGROUND
Resistance, pulse wave velocity, and wave reflections have been shown to be increased in patients with essential hypertension compared with normotensive controls. These alterations are completely normalized by nitroprusside infusion but exacerbated during beta-adrenergic blockade, suggesting an enhanced smooth muscle tone that is in part modulated by adrenergically mediated vasodilation. The present study was performed to examine the extent to which this apparently enhanced smooth muscle tone is a result of alpha-adrenergically mediated vasoconstriction.

METHODS AND RESULTS
Age-matched normotensive and hypertensive Chinese subjects were instrumented with catheter-tipped micromanometers and an electromagnetic flow velocity sensor positioned in the ascending aorta. Aortic impedance and wave reflection properties were obtained from Fourier analysis of the pressure and flow signals during baseline conditions, after beta-blockade with propranolol (0.15 mg/kg i.v.), and after alpha-blockade with intravenous phentolamine (range, 15-80 mg) that was sufficient to either normalize blood pressure or produce a pressure that could not be further lowered. Compared with normotensives, in the baseline state, hypertensives had elevated resistance (1,962 versus 1,268 dyne.sec/cm5, p less than 0.001), total power (1,893 versus 1,568 mW, p less than 0.08), reflected pressure wave component (25.6 versus 13.5 mm Hg, p less than 0.001), ratio of reflected to forward wave (0.65 versus 0.42, p less than 0.001), and pulse wave velocity as determined from the frequency of the first zero-crossing of impedance phase angle (4.6 versus 3.5 Hz, p less than 0.03). During combined alpha- and beta-adrenergic blockade, blood pressure decreased into the normal range (from 162/103 to 131/87 mm Hg) but was still somewhat higher than that in the normotensive subjects. Resistance (1,914 dyne.sec/cm5, p less than 0.03), reflected wave (19.5 mm Hg, p less than 0.01), and ratio of reflected to forward wave (0.61, p less than 0.001) were, however, persistently elevated above normal values.

CONCLUSIONS
alpha-Adrenergically mediated vasoconstriction cannot account for all of the hemodynamic alterations seen in essential hypertension.
Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy.
Authors: Bolognese L , Sarasso G , Bongo A S , Rossi L , Aralda D , Piccinino C , Rossi P 
Published: June 2012

BACKGROUND
We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy.

METHODS AND RESULTS
Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13-segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1-3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01).

CONCLUSIONS
DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention.