bluuebunny/crossref_metadata_2025 huggingface dataset:
Early evidence of endothelial vasodilator dysfunction at coronary branch points.
Authors: McLenachan J M , Vita J , Fish D R , Treasure C B , Cox D A , Ganz P , Selwyn A P
Published: June 2011

Intracoronary acetylcholine produces endothelium-dependent dilation of normal coronary arteries and paradoxical constriction of atherosclerotic vessels. Regional differences in endothelium-dependent vasomotion, however, have not been studied in relation to the nonuniform development of atherosclerosis. We compared the vasomotor response to increasing doses of acetylcholine of angiographically smooth coronary artery segments prone to atherosclerosis (coronary branch points) with segments remote from branch points (straight segments). In patients with entirely smooth coronary arteries and a dilator response to acetylcholine (group 1, n = 7), branch points and straight segments demonstrated equal and significant dose-dependent dilation to acetylcholine (14.7 +/- 8.9% and 12.3 +/- 12.7%, respectively; p identical to NS). In patients with early atherosclerosis as manifest by luminal coronary irregularities, the lowest dose of acetylcholine (10(-8) M) produced constriction at branch points and slight dilation at straight segments (-6.3 +/- 7.4% vs. +2.2 +/- 7.3%, p less than 0.05). At higher doses of acetylcholine, both branch point and straight segments constricted, but constriction remained more pronounced at branch points. Both branch point and straight segments, however, retained the ability to dilate to the non-endothelium-dependent agent, nitroglycerin. In a third group of patients with angiographically entirely smooth coronary arteries but without dilation to acetylcholine, constriction to acetylcholine again occurred first at branch points. Thus, coronary branch points demonstrate increased sensitivity to acetylcholine-induced constriction in patients with angiographic evidence of early coronary atherosclerosis and in middle-aged patients with smooth coronary arteries. These segments, however, retain the ability to dilate to nitroglycerin. Whether this early evidence of defective endothelium-dependent vasodilation predicts the later development of occlusive atherosclerosis is not yet known.
Converting enzyme inhibition prevents the effects of atrial natriuretic factor on baroreflex responses in humans.
Authors: Volpe M , Lembo G , Condorelli G , De Luca N , Lamenza F , Indolfi C , Trimarco B
Published: June 2011

The aim of this study was to assess the influence of atrial natriuretic factor (ANF) on arterial baroreflex chronotropic responses and to investigate whether this effect of ANF is affected by angiotensin converting enzyme inhibition (CEI). For this purpose, in 13 normal volunteers, the reflex chronotropic responses to arterial baroreceptor stimulation (phenylephrine, 25-100 micrograms i.v.) or deactivation (nitroglycerin, 25-100 micrograms i.v.) were evaluated in control conditions and during the steady-state phase of a sustained infusion of ANF (50 ng/kg/min) or placebo, before and during prolonged treatment with the converting enzyme inhibitor enalapril (20 mg p.o. for 5 days). ANF infusion, which raised plasma ANF levels from 48 +/- 19 to 1,765 +/- 203 pg/ml, was associated with a slight decrease in systemic blood pressure and no change in heart rate. In addition, it caused a significant increase of the regression slope obtained with phenylephrine (from 11.3 +/- 2 to 18.5 +/- 2 msec/mm Hg) and a significant reduction of slope of the nitroglycerin-produced regression line (from 9.3 +/- 1 to 5.6 +/- 0.6 msec/mm Hg). After sustained CEI, which raised plasma renin activity from 1.4 +/- 0.4 to 19.9 +/- 5 ng/ml/hr, ANF infusion induced an increase in plasma ANF levels and a reduction in blood pressure comparable to those observed in control conditions. During CEI, however, ANF infusion had no significant effect on the chronotropic baroreflex responses produced by phenylephrine or nitroglycerin. Chronotropic and pressor responses to cold exposure were unchanged after CEI and during ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiopulmonary receptor reflexes in normotensive athletes with cardiac hypertrophy.
Authors: Giannattasio C , Seravalle G , Bolla G B , Cattaneo B M , Cléroux J , Cuspidi C , Sampieri L , Grassi G , Mancia G
Published: June 2011

Cardiopulmonary receptor control of the circulation is impaired in a variety of diseases having cardiac hypertrophy as a common feature. Whether this also occurs in the so-called "physiological" cardiac hypertrophy of the athlete, however, is unknown. We studied nine sedentary healthy subjects and 19 age-matched professional runners or hammer throwers who had trained at least 2 hours per day, 5 days per week for 7 years. The left ventricular mass index (echocardiography) was 99 +/- 7.4 and 135 +/- 5.9 g/m2 in the two groups, respectively. Cardiopulmonary receptor stimulation and deactivation were obtained by increasing and reducing left ventricular end-diastolic diameter for 5 minutes by leg raising and lower body negative pressure, keeping both stimuli at a level not affecting blood pressure and heart rate. In the sedentary healthy subjects, forearm vascular resistance (the ratio between mean arterial pressure and forearm blood flow) and plasma norepinephrine fell during leg raising (forearm vascular resistance, -7 +/- 1.7 units; norepinephrine, -57.4 +/- 1.4 pg/ml) and increased during lower, body negative pressure (forearm vascular resistance, 20 +/- 5.3 units; norepinephrine, 97.7 +/- 21.5 pg/ml). For similar or greater alterations in left ventricular end-diastolic diameter, the correspondent changes observed in the professional runners or hammer throwers were -5.3 +/- 1.3 units (forearm vascular resistance), -35.4 +/- 9.6 pg/ml (norepinephrine), 9.1 +/- 1.4 units (forearm vascular resistance), and 30.9 +/- 6.9 pg/ml (norepinephrine). This represented an attenuation of 25%, 38%, 55%, and 68%, respectively (p less than 0.01), of the control response.(ABSTRACT TRUNCATED AT 250 WORDS)
Fibrillar collagen and remodeling of dilated canine left ventricle.
Authors: Weber K T , Pick R , Silver M A , Moe G W , Janicki J S , Zucker I H , Armstrong P W
Published: June 2011

To test the hypothesis that in the failing volume-overloaded ventricle, the extracellular matrix and fibrillar collagen in particular are major determinants of the architectural remodeling of the myocardium, this histopathological study of the dilated, postmortem canine left ventricle secondary to rapid ventricular pacing or aortocaval fistula was undertaken. Using the picrosirius-polarization technique to enhance collagen birefringence, we sought to examine the structural integrity of the collagen matrix and interstitium. In the dilated failing ventricle secondary to rapid pacing, we found 1) interstitial edema and a disruption or disappearance of collagen fibers that were apparent within 6 hours of pacing, persisted for weeks, and subsequently were associated with muscle fiber disorganization within the endomyocardium, 2) interstitial fibrosis that was present in the midwall and epimyocardium with chronic pacing, and 3) an early remodeling of intramyocardial coronary arteries that included medial swelling with smooth muscle degeneration followed by proliferative lesions involving fibroblasts and a subsequent perivascular and medial fibrosis. Many of these findings were still evident 48 hours after pacing had been discontinued. In contrast, the collagen matrix and interstitium seen with ventricular dilatation secondary to the circulatory overload that accompanies an aortocaval fistula were indistinguishable from that in sham-operated controls. Thus, we conclude that unlike the chamber enlargement and preserved ventricular function that accompany an aortocaval fistula, ventricular dilatation and failure caused by rapid pacing are based on an architectural remodeling of the myocardium. This structural dilatation involves the extracellular matrix and interstitium and appears to be related to altered permeability of intramyocardial coronary arteries. The mechanism or mechanisms involved in the pathogenesis of myocardial remodeling with rapid ventricular pacing require further investigation.
Quantification of area at risk during coronary occlusion and degree of myocardial salvage after reperfusion with technetium-99m methoxyisobutyl isonitrile.
Authors: Sinusas A J , Trautman K A , Bergin J D , Watson D D , Ruiz M , Smith W H , Beller G A
Published: June 2011

Serial myocardial imaging with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) has been proposed for evaluating myocardial salvage after reperfusion. To define 99mTc-MIBI uptake before and after reperfusion, 17 open-chest dogs underwent 3 hours of left anterior descending artery occlusion and 3 hours of reperfusion. 99mTc-MIBI was injected during occlusion (group 1) or after 90 minutes of reperfusion (group 2). Myocardial 99mTc-MIBI activity was correlated with microsphere flow during occlusion and reperfusion. Anatomic risk area and infarct area were defined by postmortem vital staining and correlated with the perfusion defects defined by analysis of 99mTc-MIBI macroautoradiographs and gamma camera images of myocardial slices. The left ventricle was divided into 96 segments for gamma well counting. Flow and 99mTc-MIBI activity were normalized to nonischemic values. Myocardial segments were grouped, based on occlusion flow, into zones: severely ischemic (less than or equal to 30% nonischemic), moderately ischemic (greater than 30%, less than or equal to 60% nonischemic), mildly ischemic (greater than 60%, less than or equal to 90% nonischemic), and nonischemic (greater than 90%, less than or equal to 120% nonischemic). Among dogs injected with 99mTc-MIBI during coronary occlusion (group 1), myocardial 99mTc-MIBI activity correlated linearly with occlusion flow for both endocardial (r = 0.91) and transmural (r = 0.91) segments. The risk area defined by 99mTc-MIBI autoradiography (group 1) correlated with the postmortem risk area (rho = 0.94) but was 29% smaller than the anatomic risk area (p = 0.03), reflecting the contribution of collateral flow. Among dogs injected with 99mTc-MIBI after reperfusion (group 2), myocardial 99mTc-MIBI did not correlate with reperfusion flow in either endocardial or transmural segments. Among group 2 dogs, myocardial 99mTc-MIBI activity was significantly less than reperfusion flow at the time of injection in the severely ischemic (25 +/- 5% versus 74 +/- 24% nonischemic, p = 0.002), moderately ischemic (54 +/- 12% versus 96 +/- 15% nonischemic, p = 0.001), and mildly ischemic (84 +/- 6% versus 93 +/- 3% nonischemic, p = 0.002) zones. The defect area defined by 99mTc-MIBI autoradiography (group 2) correlated very closely with the postmortem infarct area (rho = 0.98). Thus, the myocardial uptake of 99mTc-MIBI during coronary occlusion correlates with occlusion flow and reflects the "area at risk." When 99mTc-MIBI was given after 90 minutes of reperfusion following 3 hours of coronary occlusion, the myocardial activity was significantly reduced compared with reperfusion flow in both necrotic and perinecrotic regions, reflecting myocardial viability more than the degree of reperfusion.
Determination of coronary flow reserve by parametric imaging.
Authors: Hess O M , McGillem M J , DeBoe S F , Pinto I M , Gallagher K P , Mancini G B
Published: June 2011

Nine mongrel dogs were instrumented with electromagnetic flow probes (EMF) to measure coronary blood flow through the left anterior descending (LAD) and left circumflex (LCx) coronary arteries at rest and after maximal coronary vasodilation (1 mg/kg/min adenosine). Relative coronary blood flow was determined by parametric imaging in the left posterior oblique projection using digital subtraction angiography (DSA). Transmural myocardial perfusion of the LAD and LCx beds was determined with tracer-labeled microspheres. Coronary flow reserve (maximal coronary blood flow divided by resting blood flow) was calculated under control conditions and after constriction of the proximal LAD or LCx by a screw occluder. Heart rate decreased significantly from 140 beats/min at rest to 122 beats/min after adenosine (p less than 0.001) and from 134 (rest) to 120 beats/min (adenosine; p less than 0.05) after coronary constriction. Peak systolic pressure was kept constant with an aortic constrictor. Left ventricular end-diastolic pressure increased significantly from 18 mm Hg at rest to 23 mm Hg (p less than 0.05) after coronary constriction. At baseline, coronary flow reserve was 4.2 with DSA, 3.8 with EMF, and 3.7 with microspheres; after coronary constriction, it was 2.6 (DSA), 1.9 (EMF), and 1.5 (microspheres) (all p less than 0.001 versus baseline). Coronary blood flow showed a good correlation between EMF and microspheres (r = 0.87, p less than 0.001), with a standard error of estimate (SEE) of 0.78 ml/g/min. Coronary flow reserve also showed a good correlation between EMF and microspheres (r = 0.82, p less than 0.001), with an SEE of 0.93. There was a moderate correlation between EMF and DSA (r = 0.68, p less than 0.001), with an SEE of 1.35 (40% of mean coronary flow reserve). The correlation coefficient between microspheres and DSA was 0.54 (p less than 0.01), with an SEE of 1.46 (39% of mean coronary flow reserve). The mean difference (accuracy) and standard deviation of difference (precision) were 0.2 +/- 1.0 between EMF and microspheres, -0.1 +/- 1.4 between EMF and DSA, and -0.6 +/- 1.7 between microspheres and DSA. We conclude that determination of coronary flow reserve by parametric imaging is associated with large variations that are greater than variations also inherent in the two reference techniques. Parametric imaging allows relatively accurate assessment of coronary flow reserve (small mean difference), but precision is low (large standard deviation of mean differences).(ABSTRACT TRUNCATED AT 400 WORDS)
Creation of anastomoses between an extracardiac artery and the coronary circulation. Proof that myocardial angiogenesis occurs and can provide nutritional blood flow to the myocardium.
Authors: Unger E F , Sheffield C D , Epstein S E
Published: June 2011

The purpose of this investigation was to determine whether blood vessels could develop de novo between an extracardiac artery and a collateral-dependent zone of the heart and to quantify the nutritive blood flow afforded by the new vessels. We also adapted the preparation so that angiogenically active agents could be chronically administered directly to the site of neovascularization in subsequent studies. To induce neovascularization between a systemic artery and the coronary circulation, the left internal mammary artery (IMA) was implanted in an intramyocardial tunnel in proximity to the left anterior descending coronary artery (LAD). A tube situated in the distal IMA connected to an implanted pump provided for continuous intra-arterial infusion at the site of angiogenesis. During the same procedure, an ameroid constrictor was placed on the proximal LAD, rendering its perfusion territory collateral dependent during a 2-3 week period. After 8 weeks, the functional capacity of the anastomoses established between the implanted IMA and the LAD territory was assessed by determining regional myocardial blood flow under basal conditions, during adenosine-induced vasodilatation, and during differential occlusions of the IMA and left circumflex coronary artery (LCCA). For all dogs, IMA occlusion decreased maximal LAD territory flow from 1.31 +/- 0.11 to 1.16 +/- 0.10 ml/min/g (p less than 0.005). Occlusion of the LCCA decreased LAD zone flow to 0.73 +/- 0.12 ml/min/g, whereas occlusion of the IMA in addition to the LCCA further decreased LAD zone flow to 0.42 +/- 0.11 ml/min/g (p less than 0.02). The IMA provided measurable nutritive blood flow in seven of 12 dogs, and in these dogs, the artery provided 30.0 +/- 2.5% of total LAD zone collateral conductance under conditions of maximal vasodilatation (range, 23-42%). We conclude that angiogenesis can occur between an implanted internal mammary artery and the native coronary circulation in dogs, providing modest nutritive blood flow to a collateral-dependent region. Further studies will be necessary to determine whether direct, local infusion of angiogenically active factors can enhance neovascularization and whether sufficient flow can be reliably supplied to make some variant of this approach clinically applicable.
Discrepancies between Doppler and catheter gradients in aortic prosthetic valves in vitro. A manifestation of localized gradients and pressure recovery.
Authors: Baumgartner H , Khan S , DeRobertis M , Czer L , Maurer G
Published: June 2011

To evaluate possible causes of discrepancy between Doppler and catheter gradients across prosthetic valves, five sizes (19-27 mm) of St. Jude and Hancock valves were studied in an aortic pulsatile flow model. Catheter gradients at multiple sites distal to the valve were compared with simultaneously obtained Doppler gradients. In the St. Jude valve, significant differences between Doppler and catheter gradients measured 30 mm downstream from the valve were found: Doppler gradients exceeded peak catheter gradients of 10 mm Hg or more by 81 +/- 35% (15 +/- 3.6 mm Hg), and mean catheter gradients by 71 +/- 11% (10.3 +/- 2.5 mm Hg). When the catheter was pulled back through the tunnel-like central orifice of the valve, high localized gradients at the valve plane and significant early pressure recovery were found. When the catheter was pulled back through the large side orifices, gradients at the same level were only 46 +/- 6% of the central orifice gradients (mean difference, 7.6 +/- 4.5 mm Hg). Doppler peak and mean gradients showed excellent agreement with the highest central orifice catheter gradients (mean difference, 1.0 +/- 3.1 and 0.9 +/- 1.5 mm Hg, respectively). A significantly better agreement between Doppler and catheter gradients at 30 mm was found for the Hancock valve, although Doppler peak and mean gradients were still slightly greater than catheter gradients. Doppler gradients exceeded catheter gradients by 18 +/- 10% (3.4 +/- 1.9 mm Hg) and 13 +/- 11% (2.1 +/- 0.9 mm Hg), respectively. When the catheter was pulled back through the valve, the highest gradients were found approximately 20 mm distal to the valve ring.(ABSTRACT TRUNCATED AT 250 WORDS)
Noninvasive quantification of muscarinic receptors in vivo with positron emission tomography in the dog heart.
Authors: Delforge J , Janier M , Syrota A , Crouzel C , Vallois J M , Cayla J , Lançon J P , Mazoyer B M
Published: June 2011

The in vivo quantification of myocardial muscarinic receptors has been obtained in six closed-chest dogs by using positron emission tomography. The dogs were injected with a trace amount of 11C-labeled methylquinuclidinyl benzilate (MQNB), a nonmetabolized antagonist of the muscarinic receptor. This was followed 30 minutes later by an injection of an excess of unlabeled MQNB (displacement experiment). Two additional injections of unlabeled MQNB with [11C]MQNB (coinjection experiment) and without [11C]MQNB (second displacement experiment) were administered after 70 and 120 minutes, respectively. This protocol allowed a separate evaluation of the quantity of available receptors (B'max) as well as the association and dissociation rate constants (k+1 and k-1) in each dog. The parameters were calculated by using a nonlinear mathematical model in regions of interest over the left ventricle and the interventricular septum. The average value of B'max was 42 +/- 11 pmol/ml tissue, the rate constants k+1, k-1, and Kd were 0.6 +/- 0.1 ml.pmol-1.min-1, 0.27 +/- 0.03 ml.pmol-1.min-1, and 0.49 +/- 0.14 pmol.ml-1, respectively, taking into account the MQNB reaction volume estimated to 0.15 ml/ml tissue. Although [11C]MQNB binding would appear irreversible, our findings indicate that the association of the antagonist is very rapid and that the dissociation is far from negligible. The dissociated ligand, however, has a high probability of rebinding to a free receptor site instead of escaping into the microcirculation. We deduce that the positron emission tomographic images obtained after injecting a trace amount of [11C]MQNB are more representative of blood flow than of receptor density or affinity. We also suggest a simplified protocol consisting of a tracer injection of [11C]MQNB and a second injection of an excess of cold MQNB, which is sufficient to measure B'max and Kd in humans.
Blood pressure level, trend, and variability in Dunedin children. An 8-year study of a single birth cohort.
Authors: St George I M , Williams S M , Silva P A
Published: June 2011

In a birth cohort of children in the Dunedin Multidisciplinary Health and Development Study in New Zealand, resting blood pressures were recorded biennially five times from age 7 to 15 years. Using previously described methods, we examined the level, trend, and variability of blood pressures in those children with at least three readings. The level, trend, and variability of height, weight, and body mass index were compared among six separate groups of children. Two groups were categorized on the basis of high systolic pressure levels, one with low variability and the other with high variability, which was thought to resemble adult labile hypertension. Two additional groups were categorized on the basis of increasing and decreasing blood pressure trends; the fifth group had consistently low blood pressures, and the sixth group consisted of the remaining children. There were significant differences among the groups for the level of all the physical measurements and for the trend of body mass index. No significant differences were found among the groups for gender or socioeconomic status. A parental history of high blood pressure, stroke, or heart attack was significantly more common in the first two groups.
Vascular reactivity after balloon angioplasty in an atherosclerotic rabbit.
Authors: La Veau P J , Sarembock I J , Sigal S L , Yang T L , Ezekowitz M D
Published: June 2011

Alterations in vessel wall reactivity (VR) at or adjacent to the dilation site after balloon angioplasty (BA) may vary according to the inflation protocol and the time after angioplasty and may influence outcome. In 64 atherosclerotic rabbit femoral arteries, we evaluated VR after BA with intravenous ergonovine (ERGO) (40 micrograms/min for 5 minutes) and intra-arterial nitroglycerin (NTG) (2,500 micrograms single bolus) 24-72 hours and 28 days after BA. Comparisons were made with atherosclerotic, nonangioplastied, age-matched controls. BA was standardized to three 1-minute inflations, each 1 minute apart. For each balloon size, 2.5- (appropriate size) or 3.0-mm (oversized) vessels were allocated to either 5 or 10 atm inflation pressure. For the analysis, four groups were compared: Group 1, 3.0/5; group 2, 3.0/10; group 3, 2.5/5, and group 4, 2.5 mm/10 atm. Angiographic diameters were measured at, proximal, and distal to the lesion at baseline, 10 minutes after ERGO, and 5 minutes after NTG. Angiograms were measured with electronic calipers by two blinded observers. All segments of control vessels vasoconstricted to ERGO and vasodilated to NTG (p less than 0.05 versus baseline), indicating a normal response. At 24-72 hours after dilatation, the angioplasty sites for all inflation pressure/balloon size combinations were not responsive to either ERGO or NTG. All segments distal to the dilatation sites vasoconstricted to ERGO and dilated to NTG (p less than 0.05 versus baseline), indicating a normal response. Proximal segments of vessels dilated with a 2.5-mm balloon (appropriate size) responded positively to both stimuli (p less than 0.05). Those vessels dilated with a large balloon (3.0 mm) were nonreactive in the segment proximal to the angioplasty site. Twenty-eight days later angioplasty sites dilated with a 2.5-mm balloon (appropriately sized) regained reactivity; however, segments dilated with a large balloon (3.0 mm) remained unresponsive. All proximal segments, including those from vessels dilated with a large balloon, reacted positively. All distal segments reacted appropriately. Restenosis rates were not different between the over- and appropriately sized balloon groups. These data demonstrate that immediately after angioplasty, vessels lose reactivity at the dilatation site. Those vessels dilated with the smaller-size balloon (2.5 mm) regained reactivity. For large balloons, reactivity is not regained at 28 days. For segments proximal to the site of dilatation, transient loss of reactivity is seen only when a large balloon is used. Thus, acute closure originating at the site of dilatation is not a result of spasm.(ABSTRACT TRUNCATED AT 400 WORDS)
Intermittent claudication, heart disease risk factors, and mortality. The Whitehall Study.
Authors: Smith G D , Shipley M J , Rose G
Published: June 2011

In the Whitehall study, 18,388 subjects aged 40-64 years completed a questionnaire on intermittent claudication. Of these subjects, 0.8% (147) and 1% (175) were deemed to have probable intermittent claudication and possible intermittent claudication, respectively. Within the 17-year follow-up period, 38% and 40% of the probable and possible cases, respectively, died. Compared with subjects without claudication, the probable cases suffered increased mortality rates due to coronary heart disease and cerebrovascular disease, but the mortality rate due to noncardiovascular causes was not increased. Possible cases demonstrated increased mortality rates due to cardiovascular and noncardiovascular causes. This difference in mortality pattern may be due to chance. Possible and probable cases still showed increased cardiovascular and all-cause mortality rates after adjusting for coronary risk factors (cardiac ischemia at baseline, systolic blood pressure, plasma cholesterol concentration, smoking behavior, employment grade, and degree of glucose intolerance). Intermittent claudication is independently related to increased mortality rates. It is not a rare condition, and simple questionnaires exist for its detection. The latter can be usefully incorporated in cardiovascular risk assessment and screening programs.
A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis.
Authors: Waters D , Lespérance J , Francetich M , Causey D , Théroux P , Chiang Y K , Hudon G , Lemarbre L , Reitman M , Joyal M
Published: June 2011

To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 month of coronary arteriography to participate in double-blind therapy with a placebo or nicardipine 30 mg three times daily. Coronary events (5 deaths, 22 myocardial infarctions, and 28 unstable anginas) occurred in 28 of 192 nicardipine patients and 23 of 191 placebo patients (p = NS). At 24 months coronary arteriography was repeated in 335 patients. Progression, defined as a 10% or more worsening in diameter stenosis, measured quantitatively, was found in 147 of 1,153 lesions (12.7%) in 168 nicardipine patients and in 170 of 1,170 lesions (14.5%) in 167 placebo patients (p = NS). Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p = NS). Regression, that is, an improvement by 10% or more in diameter stenosis, was seen in 140 of 2,323 lesions (6.0%) overall, with no significant intergroup difference. Among the 217 patients with 411 stenoses of 20% or less in the first study, such minimal lesions progressed in only 15 of 99 nicardipine patients compared with 32 of 118 placebo patients (15% versus 27%, p = 0.046). In this subgroup, 16 of 178 minimal lesions in nicardipine patients and 38 of 233 minimal lesions in placebo patients progressed (p = 0.038). By stepwise logistic-regression analysis, baseline systolic blood pressure (p = 0.04) and the change in systolic blood pressure between baseline and 6 months (p = 0.002) correlated with progression of minimal lesions. This suggested blood pressure reduction may account for the beneficial action of nicardipine. These results suggested nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of minimal lesions.
Inotropic effects of angiotensin II on human cardiac muscle in vitro.
Authors: Moravec C S , Schluchter M D , Paranandi L , Czerska B , Stewart R W , Rosenkranz E , Bond M
Published: June 2011

The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure.
Functional chiral asymmetry in descending thoracic aorta.
Authors: Frazin L J , Lanza G , Vonesh M , Khasho F , Spitzzeri C , McGee S , Mehlman D , Chandran K B , Talano J , McPherson D
Published: June 2011

To determine whether rotational blood flow or chiral asymmetry exists in the human descending thoracic aorta, we established the ability of color Doppler ultrasound to detect rotational flow in a tornado tube model of a vortex descending fluid column. In a model of the human aortic arch with a pulse duplicator, color Doppler was then used to demonstrate that rotational flow occurs first in the transverse arch and then in the proximal descending thoracic aorta. With the use of color Doppler esophageal echocardiography, 53 patients (age range, 25-78 years; mean age, 56.4 years) were prospectively examined for rotational flow in the descending thoracic aorta. At 10 cm superior to retro-left ventricular position, 22 of 38 patients (58%) revealed rotational flow with obvious diastolic counterclockwise rotation but less obvious systolic clockwise rotation. At 5 cm superior to retro-left ventricular position, 29 of 46 patients (63%) revealed rotational flow with a tendency toward systolic clockwise and diastolic counterclockwise rotation. At the retro-left ventricular position, 47 of 53 patients (89%) revealed rotational flow, usually of a clockwise direction, occurring in systole. Our data suggest that aortic flow is not purely pulsatile and axial but has a rotational component. Rotational flow begins in the aortic arch and is carried through to the descending thoracic aorta, where flow is chirally asymmetric with systolic clockwise and diastolic counterclockwise components. These data demonstrate an aortic rotational flow component that may have physiological implications for organ perfusion.
Airway hyperresponsiveness in patients with microvascular angina. Evidence for a diffuse disorder of smooth muscle responsiveness.
Authors: Cannon R O , Peden D B , Berkebile C , Schenke W H , Kaliner M A , Epstein S E
Published: June 2011

Anginal chest pain in patients with angiographically normal coronary arteries may be caused by a limited coronary flow response to stress because of abnormal function of the coronary microcirculation (microvascular angina). Studies of forearm arterial function suggested that patients with microvascular angina may have a diffuse disorder of smooth muscle tone. Because dyspnea is common in these patients and seems disproportionate to the severity of myocardial ischemia, we studied air flow (forced expiratory volume in 1 second, or FEV1) in the basal state and after methacholine inhalation to determine whether bronchial smooth muscle is affected in this syndrome. Five of 36 patients with microvascular angina had a basal FEV1 of less than 70% of that predicted and did not receive methacholine. Of the remaining 31 patients, 14 (45%) had a more-than-20% reduction in FEV1 after methacholine inhalation (as much as 25 mg/ml), a response significantly greater than that of nine patients with heart disease (0%, p less than 0.025) and 24 normal volunteers of similar age and gender distribution (13%, p less than 0.025). Furthermore, the product of the methacholine dose inhaled and the magnitude of decline in FEV1 from baseline (methacholine response score) was significantly lower in patients with microvascular angina than in normal volunteers (16 +/- 8.6 versus 22.2 +/- 3.7, p = 0.026). We conclude that airway hyperresponsiveness is frequently demonstrable in patients with microvascular angina; these findings are consistent with our hypothesis that this syndrome may represent a more generalized abnormality of vascular and nonvascular smooth muscle function.
Effects of brief coronary occlusion and reperfusion on porcine coronary artery reactivity.
Authors: Headrick J P , Angello D A , Berne R M
Published: June 2011

The loss of coronary vasodilator reserve after ischemia-reperfusion may be due to endothelial injury, and this vascular dysfunction may contribute to functional alterations observed after ischemia. To determine whether endothelial dysfunction occurs after relatively brief periods of moderate low-flow ischemia in vivo, open-chest swine were subjected to 15 minutes of critical, subtotal left anterior descending coronary artery occlusion (80%) followed by 60 minutes of reperfusion. Serial measurements of regional coronary flow were made with the radiolabeled microsphere technique. After 60 minutes of reperfusion, the left anterior descending coronary artery was excised together with a section of the normally perfused left circumflex coronary artery to examine in vitro the relaxations to the endothelium-dependent dilators ADP and bradykinin and to the endothelial-independent dilators sodium nitroprusside and adenosine. Contractions to serotonin in quiescent rings were also examined. Endocardial and transmural blood flows recovered to preocclusion levels within 60 minutes of reperfusion, as did the epicardial-to-endocardial ratio. Vascular responses in isolated, reperfused left anterior descending coronary artery rings were significantly different from responses in control left circumflex coronary artery rings. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin were significantly depressed in the left anterior descending coronary artery rings compared with left circumflex coronary artery rings (p less than 0.05). Serotonin-induced contractions were significantly greater in occluded-reperfused left anterior descending than in left circumflex coronary arteries (p less than 0.05). Relaxations to adenosine and sodium nitroprusside were not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased endothelin in experimental heart failure.
Authors: Margulies K B , Hildebrand F L , Lerman A , Perrella M A , Burnett J C
Published: June 2011

Recent studies demonstrate that endothelin, a potent endogenous vasoconstrictor peptide, circulates in plasma of normal animals and humans. However, the role of this peptide in pathophysiological states remains unclear. The present study was designed to test the hypothesis that circulating endothelin concentrations are increased in experimental congestive heart failure (CHF), a pathophysiological state characterized by activation of vasoconstrictor mechanisms. In anesthetized dogs with CHF produced by 8 days of rapid ventricular pacing (n = 28), circulating plasma endothelin was increased compared with values for normal controls (n = 28; 20.4 +/- 1.4 versus 9.7 +/- 0.9 pg/ml, respectively; p less than 0.0001). A plasma endothelin level of more than 14.0 was a sensitive and specific indicator of significant CHF. Moreover, within the group with experimental CHF, right atrial pressure and pulmonary capillary wedge pressure correlated independently with circulating endothelin levels. Based on recent studies demonstrating the physiological actions of twofold increases in circulating endothelin, as observed in the present study, a possible role for endothelin in the pathophysiology of CHF is advanced.
Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias.
Authors: Colatsky T J , Follmer C H , Starmer C F
Published: June 2011

Although work on class III antiarrhythmics remains at an early stage, these agents still appear to possess greater efficacy and less proarrhythmia than conventional class I agents in those experimental arrhythmia models considered to be most representative of the clinical situation. Although prolongation of repolarization carries with its own tendency for pause-dependent arrhythmogenesis (i.e., torsade de pointes), available data suggest that this may be a function of nonspecificity in potassium channel block rather than a general characteristic of class III activity. The availability of new and more selective blockers of specific cardiac potassium channels under development as class III agents have already helped to clarify basic questions about the ionic mechanism of repolarization in the heart, and one hopes that a growing clinical data base will eventually determine the relative safety and efficacy of these agents in preventing symptomatic and life-threatening arrhythmias.
Metabolic Changes in Response to Acute Cerebral Ischemia Following Unilateral Carotid Artery Ligation in Arteriosclerotic Versus Nonarteriosclerotic Rats
Authors: WEXLER BERNARD C. , SAROFF JACK
Published: June 2011

The left carotid artery of arteriosclerotic and nonarteriosclerotic male and female rats was surgically ligated to induce a state of cerebral ischemia. The animals promptly developed signs of cerebral impairment and were sacrificed 2, 4, 6, 8, 10, 12, 24, and 48 hours later to determine what dynamic pathophysiological changes attend acute cerebral ischemia.

Several of the arteriosclerotic animals developed myocardial infarcts concomitant with the cerebral edema, hemorrhage, necrosis, and leptomeningitis observed in general. All of the experimental animals manifested necrosis and fatty infiltration of the liver, and their adrenal glands were hypertrophied, hemorrhagic, and depleted of lipid.

Serum creatine phosphokinase and glutamic oxalacetic transaminase rose abruptly after 24 hours of cerebral ischemia. Triglycerides, free fatty acids, and cholesterol alterations were in keeping with intense lipid mobilization, dissolution of peripheral adipose tissue sites, and fatty metamorphosis of the liver. The animals also showed marked hyperglycemia and increased secretion of corticosterone. These investigations indicate that acute cerebral ischemia is a severe stress and will elicit dynamic alterations in serum parameters such as enzymes, lipids, glucose, and the adrenocortical stress hormones. Animals with pre-existing arteriosclerosis manifest more untoward effects and greater excursion in serum metabolic parameters than nonarteriosclerotic subjects.
Pathogenesis of Cerebral Infarction Secondary to Mechanical Carotid Artery Occlusion
Authors: LANDOLT ALEX M. , MILLIKAN CLARK H.
Published: June 2011

The immediate postoperative cerebral complications of 65 carotid occlusions were evaluated. The occlusions were done in all but one case for intracranial saccular aneurysms and were performed by either direct ligation (quick type) or slow turning down of a Silverstone clamp or similar device (slow occlusion). Cerebral complications occurred in 21 patients. The quick type of occlusion of the artery resulted in a complication rate of 24% whereas the slow type had a rate of 38%. A total of 123 cases involving cerebral complications after carotid ligation were collected from the literature and evaluated. The combined total of 81 cases of transient complications that were collected from the literature and from our series showed that such deficits occur frequently from 10 minutes to six hours after the occlusion of the vessel.
Physical Factors in the Pathogenesis of Cerebral Atherosclerosis
Authors: RESCH JOSEPH A. , LOEWENSON RUTH B. , BAKER A. B.
Published: June 2011

This report consists of an analysis of autopsy material from 5,031 cases. The cerebral vessels, as represented by the circle of Willis, were scored for severity and extent of atherosclerosis. The effect of physical factors on this process was considered. It is concluded from our data that LaPlace's law best explains the mechanical stress leading to injury of the vessel wall. The literature concerning this and other hypotheses is reviewed.
Nationwide Cerebrovascular Disease Morbidity Study
Authors: KULLER LEWIS , ANDERSON HERBERT , PETERSON DONALD , CASSEL JOHN , SPIERS PHILLIP , CURRY HIRAM , PAEGEL BERTHA , SASLAW MILTON , SISK CHARLES , WILBER JOSEPH , MILLWARD DAVID , WINKELSTEIN WARREN , LILIENFELD ABRAHAM , SELSTER RAYMOND
Published: June 2011

Previous studies have noted that the geographic differences in stroke mortality among areas of the United States were not due to artifacts of certification practices or accuracy of the diagnosis. A study of hospitalized stroke patients was completed in order to determine whether the mortality differences were due to a higher incidence or case fatality following a stroke in areas with high stroke death rates. Eight of the nine areas that participated in the Nationwide Mortality Study were included in this study. A total of 2,619 stroke cases were ascertained including 1,631 (62.3%) who were alive at the time of hospital discharge, 937 (35.8%) dead at discharge, 46 (1.7%) who were discharged alive but died outside of the hospital, and five (0.2%) who were dead at discharge and certified by the medical examiner.

The incidence of stroke was higher in the high stroke death rate areas especially for men. The ratio of the incidence of stroke in men as compared to women was higher in the younger age groups (45–54, 55–64) and in the high-incidence as compared to low-incidence areas.

The case-fatality percentage was lowest in Denver and highest in South Carolina. Presence of coma on admission was the principal determinant of subsequent mortality in all areas.

Finally, there was no consistent difference in the distribution of symptoms of stroke among the areas, and diagnostic procedures were performed more often in urban than rural areas. Approximately 80% of the stroke cases could be substantiated by either an autopsy verifying diagnosis, arteriography, hemorrhagic spinal fluid, hemiplegia or coma on admission. Several hypotheses to explain the differences have been suggested as well as the need for new information.
Transient Cerebral Ischemic Attacks Associated With Subacute Bacterial Endocarditis
Authors: SIEKERT ROBERT G. , JONES ROYDEN H.
Published: June 2011

The case histories are given of 12 patients who had transient cerebral attacks in association with subacute bacterial endocarditis. The attacks are similar to those that accompany atherosclerotic occlusive cerebrovascular disease. All patients had manifestations of general illness, particularly fever, malaise, and elevated sedimentation rate. Subsequently, cerebral infarcts occurred in three patients and cerebral hemorrhages in four patients. A definite relationship between anticoagulant therapy and hemorrhage could not be established.
Abnormal Hemispheric Blood Flow and Metabolism Despite Normal Angiograms in Patients with Stroke
Authors: MEYER JOHN STIRLING , SHINOHARA YUKITO , KANDA TADASHI , FUKUUCHI YASUO , KOK NORMA K. , ERICSSON ARTHUR DALE
Published: June 2011

Hemispheric blood flow (HBF) and metabolism were measured using the intracarotid injection of hydrogen-saturated saline in a group of patients with unilateral hemispheric infarction, some of whom had normal angiograms.

Blood flow was calculated from the formula derived from the Stewart-Hamilton principle using the clearance curve of hydrogen in the cerebral transverse sinus. Hemispheric metabolic index was estimated using a newly developed formula by assuming that the distribution of hydrogen into each transverse sinus following intracarotid injection indicates the distribution of blood from each hemisphere into each transverse sinus.

HBF and oxygen metabolism on the affected side were reduced in all groups, but the reduction was greater in patients with angiographical evidence of vascular occlusion.

In many patients, HBF and metabolism on the nonaffected side which angiograms showed to be normal were reduced in the acute phase.

It is apparent that by using the hydrogen bolus technique of measuring HBF and metabolism, small disturbances in cerebral circulation can be detected which are not discernible in angiograms.
Reflections on "The Subclavian Steal"
Authors: FIELDS WILLIAM S.
Published: June 2011

Reversal of blood flow in the vertebral artery, demonstrated by angiography, was reported ten years ago and immediately given the colorful name of "The Subclavian Steal." Since then, numerous articles have appeared, in English and other languages, reporting both clinical and arteriographical descriptions of the phenomenon.

A search of the literature has turned up a most interesting early report in which cerebrovascular symptoms were ascribed to the hemodynamic alterations. This case report appeared almost 100 years prior to the aforementioned article in the modern medical literature.

It was further suggested by the physician describing this case that ligature of the vertebral artery would be the treatment of choice in the relief of symptoms.
Noradrenergic Mediation of Experimental Cerebrovascular Spasm
Authors: FRASER R. A. R. , STEIN B. M. , BARRETT R. E. , POOL J. L.
Published: June 2011

Catecholamine fluorescent techniques demonstrate an abundant noradrenergic periarterial nerve plexus in the adventitia of the major intracranial vessels. After repeated spasm of these vessels, a marked reduction to complete absence of catecholamine fluorescence is noted. Seemingly, an exhaustion of noradrenalin stores from the nerve terminals has taken place. This has suggested the possibility of noradrenergic mediation of cerebrovascular spasm. Pharmacological depletion of the noradrenalin stores of this plexus produces a dilated vessel, but blood-induced vasospasm is not prevented. Alpha adrenergic blockade at the receptor prevents the induction of vasospasm and dilates both normal and spastic vessels above normal caliber.

These data suggest that cerebral vasospasm is produced by substances acting at the alpha adrenergic receptor of the vessel wall, and that blood contains a vasoconstrictor substance capable of acting at the receptor site.