bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of Doppler flow velocity measurement to assess the hemodynamic response to vasodilators in patients with heart failure.
Authors: Elkayam U , Gardin J M , Berkley R , Hughes C A , Henry W L
Published: June 2011

To determine if the hemodynamic response to vasodilator therapy can be assessed noninvasively by pulsed Doppler velocimetry, we compared the hemodynamic changes after treatment to changes in Doppler aortic blood flow measurements. The relationship between the absolute values and percent changes of invasively measured systemic vascular resistance (SVR) and stroke volume (SV) and Doppler-measured peak flow velocity (PFV), left ventricular ejection time (ET) and flow velocity integral (FVI) were evaluated. Measurements were made during 18 drug interventions in 13 patients treated with vasodilator agents for congestive heart failure (CHF). A poor correlation was found between the absolute values of either SVR or SV and the absolute values of each of the three Doppler aortic blood flow indexes studied. In contrast, a good correlation was found between percent changes in aortic PFV and in SVR (r = -0.89), and between percent changes in Doppler aortic FVI and in SV (r = 0.88). The correlation between percent changes in SVR and FVI revealed an r value of -0.65, while the correlation between percent changes in SVR and in ET showed an r value of -0.15. Percent changes in SV and either PFV or ET correlated with r values of 0.75 and 0.70, respectively. We conclude that Doppler aortic blood flow measurement can be used to assess quantitative changes in SVR and SV after vasodilator therapy. These findings suggest that it may be useful for evaluating vasodilator drug therapy in patients with CHF.
Severe pulmonary hypertension associated with a small ventricular septal defect.
Authors: Bisset G S , Hirschfeld S S
Published: June 2011

A case of progressive pulmonary hypertension in a child with a small ventricular septal defect is presented. Natural history studies have indicated that children with small ventricular septal defects can be followed conservatively. This case represents a contradiction to that rule and suggests that further study must be directed toward defining the etiology of pulmonary hypertension in patients with congenital heart disease.
The early recognition of right ventricular infarction: diagnostic accuracy of the electrocardiographic V4R lead.
Authors: Klein H O , Tordjman T , Ninio R , Sareli P , Oren V , Lang R , Gefen J , Pauzner C , Di Segni E , David D , Kaplinsky E
Published: June 2011

The sensitivity and specificity of ST-segment elevation in the right precordial lead V4R as an early indicator of right ventricular infarction were examined in a consecutive series of 110 patients admitted for acute inferior myocardial infarction. The sensitivity was 82.7%, the specificity 76.9% and the positive predictive value 70% in 58 patients with right ventricular infarction documented by autopsy or a combination of radionuclide ventriculography and one or more of the following tests: echocardiography, technetium-99m pyrophosphate scintigraphy and hemodynamic monitoring. The negative predictive value was 87.7%. Because of its simplicity and its high sensitivity and specificity, recording of V4R should be an intrinsic part of the early evaluation and electrocardiographic examination of acute inferior wall infarction.
Importance of left atrial function in patients with myocardial infarction.
Authors: Matsuda Y , Toma Y , Ogawa H , Matsuzaki M , Katayama K , Fujii T , Yoshino F , Moritani K , Kumada T , Kusukawa R
Published: June 2011

Left atrial function was evaluated in patients with and without remote myocardial infarction. The simultaneous left atrial pressure recording and left atrial and left ventricular cineangiograms were obtained with a catheter-tip micromanometer. The pressure-volume curve of the left atrium was composed of an A-loop and a V-loop. The ratio of active atrial emptying to left ventricular stroke volume in patients with myocardial infarction was significantly larger than that in normal subjects (42 +/- 12% vs 29 +/- 10%, p less than 0.05). The left atrial work was also significantly greater in patients with myocardial infarction (1690 +/- 717 mm Hg X ml) than in normal subjects (940 +/- 426 mm Hg X ml, p less than 0.05). The ratio of active atrial emptying to left ventricular stroke volume and left atrial work were significantly related in both normal subjects and patients with myocardial infarction (gamma = 0.72, p less than 0.01). The left ventricular ejection fraction correlated inversely with left atrial work (gamma = -0.5, p less than 0.05). Left atrial work also showed a significant linear correlation with left atrial volume before active atrial emptying (gamma = 0.82, p less than 0.01). We conclude that the left atrial contribution to left ventricular function is increased in patients with remote myocardial infarction. This left atrial contribution to the left ventricle is attributed to the Frank-Starling mechanism in the left atrium.
Hypertension reduces the number of beta-adrenergic receptors in rat brain microvessels.
Authors: Magnoni M S , Kobayashi H , Cazzaniga A , Izumi F , Spano P F , Trabucchi M
Published: June 2011

Beta-adrenergic receptor function was measured in cerebral microvessels of spontaneously and DOCA-salt hypertensive rats using 125I-iodohydroxybenzylpindolol (IHYP). Both in genetic and in experimental hypertension, a significant decrease in the number of beta-receptor sites was observed, without receptor affinity changes. These results suggest that alterations of central adrenergic regulation of small vessels may participate in the pathogenetic mechanisms leading to the development of the central hypertensive disease.
Diastolic "locking" of the mitral valve: the importance of atrial systole and intraventricular volume.
Authors: David D , Michelson E L , Naito M , Chen C C , Schaffenburg M , Dreifus L S
Published: June 2011

Diastolic mitral valve "locking," defined as sustained diastolic closure of the mitral valve after atrial systole, was investigated by simultaneous hemodynamic and echocardiographic recordings during a protocol of programmed pacing in six dogs with surgically induced atrioventricular block. Atrial extrasystoles were introduced at progressively increasing coupling intervals during programmed prolonged pauses in ventricular pacing. As the coupling interval of the atrial extrasystole was increased, both the mitral reopening time (MRT) and the calculated left ventricular volume (LVV) at the end of the MRT increased proportionally. These interrelations could be best expressed by a general logarithmic function of the form y = a + b ln (x), where x = the coupling interval of the atrial extrasystole and y = the MRT or the LVV. Correlations between the measured data and the predicted data were excellent (r greater than or equal to 0.95). In each dog, a specific LVV had to be attained to allow a diastolic "locking" of the mitral valve. Atrial standstill and atrial fibrillation were also induced in each dog to study the relative role of atrial systole in locking of the mitral valve. During either atrial standstill or atrial fibrillation, the mitral valve closed transiently, but did not lock, despite the accumulation of a LVV larger than the LVV necessary to lock the valve during sinus rhythm. Thus, diastolic locking of the mitral valve has several determinants, including the presence of active atrial systole and the accumulation of a sufficient intraventricular volume.
Catecholamine-dependent atrioventricular nodal reentrant tachycardia.
Authors: Hariman R J , Gomes J A , El-Sherif N
Published: June 2011

An unusual case of atrioventricular nodal reentrant tachycardia precipitated by ethanol ingestion is presented. Programmed atrial and ventricular stimulation failed to induce the tachycardia during control conditions or after atropine administration. This failure to induce tachycardia was related to the absence of ventriculoatrial conduction. A low-dose isoproterenol infusion allowed induction of atrioventricular nodal reentrant tachycardia by the enhancement of ventriculoatrial conduction. This report suggests that programmed stimulation during isoproterenol infusion can be used to induce paroxysmal supraventricular tachycardia in suspected cases in whom induction during control conditions or after atropine administration is not possible.
Effects of ischemic-like insult on myocardial thallium-201 accumulation.
Authors: Goldhaber S Z , Newell J B , Alpert N M , Andrews E , Pohost G M , Ingwall J S
Published: June 2011

Despite extensive clinical use of thallium-201 (201TI) for myocardial imaging, the effect of ischemia on myocardial accumulation and release of 201TI independent of flow has not been fully defined. Therefore, myocardial accumulation of 201TI in response to ischemic-like myocardial injury was assessed in vitro using the cultured fetal mouse heart preparation. Cultured fetal mouse hearts (n = 311) were subjected to injury simulating ischemia by deprivation of oxygen and oxidizable substrates for periods ranging from 15 minutes to 10 hours. The extent of irreversible injury was determined by the percentage of lactic dehydrogenase (LDH) lost from the hearts to the culture medium during recovery from injury. Injury was essentially reversible at 1 hour of insult. The fraction of 201TI content in injured compared with control hearts was not significantly lower after 1 hour of insult. By 3 hours of insult, irreversible injury as assessed by loss of LDH was detectable and the extent of injury increased progressively through 10 hours. During the 3-10-hour period of irreversible injury, 201TI accumulation within injured hearts compared with controls was related in a monotonically decreasing fashion to the loss of LDH as described by a mathematical kinetic model that fit the observations closely (R2 greater than 0.99). These results indicate that in this organ culture preparation, in which there is effectively an unlimited reservoir of 201TI and no confounding effects of perfusion, the time-dependent 201TI accumulation is determined by the extent of irreversible injury.
Correlation of echocardiographic wall stress and left ventricular pressure and function in aortic stenosis.
Authors: DePace N L , Ren J F , Iskandrian A S , Kotler M N , Hakki A H , Segal B L
Published: June 2011

Previous studies have suggested that left ventricular pressure (P) can be predicted in patients with aortic stenosis by the equation P = 235 h/r, where 235 is a constant peak wall stress (sigma), h is end-systolic wall thickness, and r is end-systolic dimension/2; h and r are measured by M-mode echocardiography. In 73 patients with aortic stenosis (valve area less than 0.7 cm2), measured and predicted left ventricular pressure correlated poorly (r = 0.17). The measured wall stress in our patients varied from 120 to 250 mm Hg in patients with normal left ventricular function and from 250 to 550 mm Hg in patients with abnormal function. The correlation between sigma and h was only fair (r = 0.53), because many patients had inappropriate left ventricular hypertrophy. There was a statistically significant correlation between ejection fraction and sigma (r = 0.62) and between ejection fraction and end-systolic dimension (r = -0.70), but there was considerable scatter of ejection fractions for any given end-systolic dimension. We conclude that sigma is not constant in aortic stenosis, and the use of a constant sigma to predict left ventricular pressure is unreliable; inappropriate left ventricular hypertrophy may explain why sigma is not constant. M-mode echocardiography is not reliable in assessing the severity of aortic stenosis in adults; such assessment requires precise measurements of pressure gradients and flow by cardiac catheterization.
Subxiphoid two-dimensional echocardiographic diagnosis of double-chambered right ventricle.
Authors: Matina D , van Doesburg N H , Fouron J C , Guérin R , Davignon A
Published: June 2011

The echocardiographic features of 14 patients with double-chambered right ventricle are presented. Diagnosis was confirmed in 13 patients at cardiac catheterization and in one at necropsy. The ultrasonic diagnosis was based on the visualization in subxiphoid short-axis view of an anomalous muscle bundle at the lower margin of the right ventricular infundibulum; this structure was present in diastole and systole and the distal portion of infundibulum was wide and free of obstruction. Associated lesions were very frequent (especially ventricular septal defects, present in 13 patients). Subxiphoid two-dimensional echocardiography is an easy, reliable, noninvasive means of assessing this disease in infants and children.
Geometric determinants of electrocardiographic left ventricular hypertrophy.
Authors: Devereux R B , Phillips M C , Casale P N , Eisenberg R R , Kligfield P
Published: June 2011

Experimental studies have suggested that electrocardiographic recognition of left ventricular hypertrophy depends on geometric relationships involving wall thickness and chamber size. To determine the clinical significance of these observations, we studied the effects of echocardiographic LV mass (LVM), posterior wall thickness (PWT), interventricular septal thickness (IVST) and internal dimension (LVID) on ECG voltage in 360 patients. Standard voltage and nonvoltage manifestations of LVH correlated modestly with LVM (r = 0.33-0.44, p less than 0.001). Sokolow-Lyon precordial voltage (SLV) (SV1 + RV5 or V6) correlated moderately with LVM (r = 0.41, p less than 0.001), but correlated less well with IVST (r = 0.26), PWT (r = 0.24) or LVID (r = 0.22). Stepwise regression revealed that there was no relation, independent of LVM, between SLV and IVST (r = 0.03), PWT (r = 0.03) or LVID (r = 0.01). The 90 patients with increased LVM (greater than 215 g) but without LVH by SLV (false negatives) were compared with the 48 identified by SLV (true positives). False negatives differed from true positives in LVM (298 +/- 72 vs 339 +/- 98 g, p less than 0.01), age (55 +/- 18 vs 44 +/- 19 years, p less than 0.001), weight (70 +/- 16 vs 63 +/- 14 kg, p less than 0.02), and distance from skin to the interventricular septum (42 +/- 10 vs 38 +/- 8 mm, p less than 0.02). Thus, for a given LVM, ECG voltage criteria of LVH are independent of LV chamber dilatation or other geometric variables, but depend on age, weight and LV depth in the chest, suggesting that stratification of subjects by clinical variables has promise for improved electrocardiographic recognition of LVH.
Echocardiographic features of a mycotic aneurysm of the left ventricular outflow tract caused by perforation of mitral-aortic intervalvular fibrosa.
Authors: Bansal R C , Moloney P M , Marsa R J , Jacobson J G
Published: June 2011

We present the apparently unique M-mode and two-dimensional echocardiographic features of a surgically confirmed pseudoaneurysm of the left ventricular outflow tract, which probably developed as a result of perforation of the mitral-aortic intervalvular fibrosa. Echocardiographic studies revealed an aneurysmal sac situated between the aortic root and the left atrium. The aneurysm expanded in systole and collapsed or emptied in diastole, suggesting direct communication with the left ventricle. Such an aneurysm must be differentiated from various pathologic findings of the aortic root. The location and characteristic motion during the cardiac cycle should alert the clinician to the correct diagnosis of such an aneurysm.
The time course and characterization of myocardial hemorrhage after coronary reperfusion in the anesthetized dog.
Authors: Higginson L A , Beanlands D S , Nair R C , Temple V , Sheldrick K
Published: June 2011

We quantitated hemorrhage associated with reperfusion after varying periods of myocardial ischemia and examined the flow characteristics that accompany reperfusion hemorrhage. Anesthetized dogs were reperfused after 2, 6 or 24 hours of circumflex occlusion. A control group underwent coronary occlusion without reperfusion. Radioactive microspheres were injected before and 5 minutes and 24 hours after reperfusion. The papillary muscles were analyzed for hemoglobin content, flow during myocardial ischemia and flow early and 24 hours after reperfusion. Myocardial creatine kinase activity was assayed to determine the severity of myocardial necrosis in the papillary muscles. Hemorrhage into the posterior papillary muscle was dependent upon the duration of coronary artery occlusion. Posterior papillary hemoglobin averaged 14 mg/g in the 2-hour group, 28 mg/g in the 6-hour group and 36 mg/g in the group reperfused 24 hours after occlusion, compared with 8.7 mg/g in the control group. Myocardial hemorrhage was associated with severe depression in myocardial CK and marked depression in flow to the ischemic area (i.e., collateral flow) during the occlusion. Early reflow averaged 112 ml/min/100 g in the 2-hour group, 61 ml/min/100 g in the 6-hour group and only 5.8 ml/min/100 g in the 24-hour group. Therefore, myocardial hemorrhage induced by reperfusion of the acutely ischemic myocardium is associated with severe ischemia during occlusion and severe myocardial necrosis, but does not depend upon the magnitude of early reflow. Myocardial hemorrhage may occur even though initial reflow values are markedly decreased.
Influence of atrial systole on the Frank-Starling relation and the end-diastolic pressure-diameter relation of the left ventricle.
Authors: Linderer T , Chatterjee K , Parmley W W , Sievers R E , Glantz S A , Tyberg J V
Published: June 2011

The influence of atrial systole on the left ventricular function curve (stroke volume vs end-diastolic pressure or end-diastolic diameter) and on the left ventricular end-diastolic pressure diameter relation was studied in nine anesthetized, open-chest dogs whose atrioventricular (AV) node had been completely blocked. Measurements were made during volume loading with the pericardium closed and opened and during alternate AV sequential pacing (to permit atrial contribution to ventricular filling) and AV simultaneous pacing (to prevent atrial contribution). When the pericardium was closed, withdrawal of the atrial contribution shifted the stroke-volume end-diastolic pressure relation downward, but did not shift the stroke volume-end-diastolic diameter relation, i.e., it reduced stroke volume for a given end-diastolic pressure according to a reduction in end-diastolic volume. The downward shift of the stroke volume-end-diastolic pressure relation was caused by an upward shift of the end-diastolic pressure-diameter relation, which, for a given end-diastolic pressure, resulted in a smaller end-diastolic diameter and, thus, in a smaller stroke volume. The reason for the upward shift in the end-diastolic pressure-diameter relation was that the atrium remained full and thus increased pericardial pressure by increasing pericardial volume. Opening the pericardium shifted the end-diastolic pressure-diameter relation downward and to the right, shifted the stroke volume-end-diastolic diameter relation upward and abolished the effect of withdrawal of the atrial contribution on these curves. We conclude that in the presence of an intact pericardium, atrial systole shifts the stroke volume-end-diastolic pressure relation because it shifts the end-diastolic pressure-diameter relation and it improves left ventricular performance by increasing preload.
The neurohumoral and hemodynamic response to orthostatic tilt in patients with congestive heart failure.
Authors: Levine T B , Francis G S , Goldsmith S R , Cohn J N
Published: June 2011

Thirty-five patients with varying degrees of congestive heart failure were subjected to 60 degrees upright tilt. Eight of the patients with normal resting hemodynamics had elevated resting plasma norepinephrine levels (PNE) (p less than 0.001), but their response to upright tilt was similar to that in normal subjects: All had increases in heart rate, plasma norepinephrine (from 263 +/- 32 to 483 +/- 78 pg/mg, p less than 0.02) and plasma renin activity (from 4.8 +/- 0.9 to 13.7 +/- 7.6 ng/ml/hour, p less than 0.05). In 27 patients with high resting pulmonary wedge pressure and low cardiac index, resting PNE was higher (668 +/- 71 ng/ml), but PNE, plasma renin activity and heart rate did not increase significantly during tilt despite a fall in pulmonary capillary wedge pressure and cardiac index. In 18 of these patients, PNE rose during tilt, whereas in nine it did not change or fell; the resting hemodynamics and the hemodynamic response to tilt were not significantly different in these two groups. These data suggest that an abnormality of mechanoreceptor or baroreceptor function is common in patients with CHF. This abnormality corresponds in part to the severity of the resting hemodynamic abnormality, but among patients with severe CHF, the reflex neurohumoral abnormality may provide independent information about the severity of the disease.
The effect of nifedipine on arterial pressure and reflex cardiac control.
Authors: McLeay R A , Stallard T J , Watson R D , Littler W A
Published: June 2011

Nine patients with untreated essential hypertension (mean casual blood pressure 173/109 +/- 14/7 mm Hg) (+/- SD) were studied in the control state and after 16 weeks of treatment with nifedipine, 10 mg orally every 8 hours. Direct arterial blood pressure monitored continuously over 24 hours showed that nifedipine significantly reduced systolic and diastolic blood pressure throughout the day and the night. The variability of blood pressure was not altered by nifedipine therapy. There was no significant change in heart rate after nifedipine therapy. Chronic nifedipine therapy increased forearm blood flow and decreased forearm vascular resistance, consistent with its action as a vasodilator. The absolute blood pressure responses to tilt, handgrip and cold were reduced, but the percent increase in pressure was not altered by therapy. Plasma renin activity was not altered by chronic nifedipine therapy. At each study, the sensitivity and setting of the baroreflex response to i.v. phenylephrine was measured. After chronic nifedipine therapy there was resetting of the sinoaortic baroreflex and an increase in its sensitivity. Successful control of blood pressure with nifedipine led to a significant reduction in the left ventricular mass index.
Exercise testing in asymptomatic or minimally symptomatic aortic regurgitation: relationship of left ventricular ejection fraction to left ventricular filling pressure during exercise.
Authors: Boucher C A , Wilson R A , Kanarek D J , Hutter A M , Okada R D , Liberthson R R , Strauss H W , Pohost G M
Published: June 2011

Exercise radionuclide angiography is being used to evaluate left ventricular function in patients with aortic regurgitation. Ejection fraction is the most common variable analyzed. To better understand the rest and exercise ejection fraction in this setting, 20 patients with asymptomatic or minimally symptomatic severe aortic regurgitation were studied. All underwent simultaneous supine exercise radionuclide angiography and pulmonary gas exchange measurement and underwent rest and exercise measurement of pulmonary artery wedge pressure (PAWP) during cardiac catheterization. Eight patients had a peak exercise PAWP less than 15 mm Hg (group 1) and 12 had a peak exercise PAWP greater than or equal to 15 mm Hg (group 2). Group 1 patients were younger and more were in New York Heart Association class I. Group 1 patients also had a higher mean rest ejection fraction (0.64 +/- 0.08 vs 0.49 +/- 0.13, p less than 0.01, higher exercise ejection fraction (0.63 +/- 0.10 vs 0.40 +/- 0.18, p less than 0.01), lower end-systolic volume (38 +/- 13 vs 79 +/- 36 ml/m2, p less than 0.01) and higher peak oxygen uptake (24.9 +/- 5.1 vs 16.6 +/- 4.9 ml/kg/min, p less than 0.01) than group 2 patients. However, the two groups had similar cardiothoracic ratios, changes in ejection fractions with exercise, and rest and exercise regurgitant indexes. Using multiple regression analysis, the best correlate of the exercise PAWP was peak oxygen uptake (r = -0.78, p less than 0.01). No other measurement added significantly to the regression. When peak oxygen uptake was excluded, rest and exercise ejection fraction also correlated significantly (r = -0.62 and r = -0.60, respectively, p less than 0.01). Patients with asymptomatic or minimally symptomatic severe aortic regurgitation have a wide spectrum of cardiac performance in terms of the PAWP during exercise. The absolute rest and exercise ejection fraction and the level of exercise achieved are noninvasive variables that correlate with exercise PAWP in aortic regurgitation, but the change in ejection fraction with exercise by itself is not.
Myocardial fiber diameter and regional distribution in the ventricular wall of normal adult hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy.
Authors: Hoshino T , Fujiwara H , Kawai C , Hamashima Y
Published: June 2011

Myocardial fiber diameters were measured to determine their distribution throughout the ventricular wall in normal adult hearts, hypertensive hearts and hearts with hypertrophic cardiomyopathy (HCM). In normal adult hearts and hypertensive hearts, the diameter decreased from the inner to the outer third of the left ventricular free wall and from the left ventricular side to the right ventricular side of the septum. In HCM, these regional differences were preserved in the left ventricular free wall, but not in the septum. The diameter was greatest in the middle third of the septum, where myocardial fiber disarray was widely distributed. The diameters of the fibers in the right ventricular side of the septum were significantly larger than those of the fibers in the left ventricular side of the septum in HCM. This finding, in contrast to that in normal adult hearts or hypertensive hearts, was considered to be related to the inward convex curvature of the left ventricular chamber. Although there was no significant difference in the diameter of myocardial fibers in the left ventricular free wall between hypertensive hearts and hearts with HCM, the diameters of those in the right ventricular free wall, in the right ventricular side of the septum and in the middle third of the septum were significantly larger in HCM than in hypertensive hearts. We conclude that there is a transmural variation of myocardial fiber diameter in the left ventricular free wall and the ventricular septum, and such transmural variation in HCM is clearly different from that in hypertensive hearts.
Topography of preemptying ventricular segments in patients with Wolff-Parkinson-White syndrome using scintigraphic phase mapping and esophageal pacing.
Authors: Chan W W , Kalff V , Dick M , Rabinovitch M A , Jenkins J , Thrall J H , Pitt B
Published: June 2011

We analyzed the sequence of ventricular emptying using the phase image in 10 patients with accessory pathways and in 15 normal subjects. In normal subjects, the earliest emptying occurred in ventricular septal, apical and left basal segments. Eight patients had manifest preexcitation; the earliest emptying occurred ectopically in the right ventricle in one of these patients and in the left ventricle in five. The remaining two patients had normal phase maps. Two patients had concealed left-sided pathways. Their phase maps showed earliest emptying in left basal segments. Six of the 10 patients underwent electrophysiologic mapping. There was complete agreement between phase and electrophysiologic maps. Transesophageal atrial pacing increased preexcitation in one patient, normalized the ECG in another and precipitated narrow QRS tachycardia in four patients. Phase maps then showed enlargement, reduction and loss of the ectopic earliest emptying segments, respectively. We conclude that this technique in conjunction with pacing is successful in lateralizing accessory pathways.
Coronary spasm and thrombosis associated with myocardial infarction in a patient with nearly normal coronary arteries.
Authors: Benacerraf A , Scholl J M , Achard F , Tonnelier M , Lavergne G
Published: June 2011

A 37-year-old man presented with an evolving inferior myocardial infarction. Coronary angiography performed within 3 hours after the onset of the pain showed spasm of the right coronary artery and the presence of intracoronary thrombi. After resolution of spasm and the disappearance of thrombi, angiography revealed nearly normal coronary arteries. An ergonovine test was positive when the patient was not taking medication and became negative when he was taking diltiazem. The course was uncomplicated, and after 9 months the patient is free of angina.
Coronary heart disease: genetic aspects.
Authors: Neufeld H N , Goldbourt U
Published: June 2011

Morbidity and mortality differences between populations, between ethnic groups and between individuals are not satisfactorily explained by the variation of risk factors. Differences in genetic susceptibility might be responsible for a part of the unexplained variation of coronary heart disease (CHD) rates. Genetic factors are also significant in determining the level of risk factors in individuals. Ample evidence links genetic factors to the levels of serum cholesterol, blood pressure and diabetes. Marked sex differences in CHD mortality also indicate the role of heredity in the development of the disease. The male:female ratio varies widely between different countries, as well as between different ethnic groups. These variations are difficult to explain by variation in environmental and behavioral differences between males and females alone. The degree of atherosclerosis in males and females varies, depending on the anatomic location of the atherosclerosis. Inherited disorders of metabolism and the variability of anatomic patterns provide additional indications of the role of genetics. The data accumulated in the Israeli Ischemic Heart Disease Study over 15 years reveal an ethnic variation of risk factors coupled with remarkably larger variation in disease rates. Patterns of incidence assessed in the national mortality data of the Israeli study and in histologic findings in the coronary arteries of infants from different ethnic groups are compatible with a hypothesis that ethnic and sex differences in early structural changes of the coronary arteries partly determine the susceptibility of the latter to the development of atherosclerosis. In conclusion, findings from our studies and the review of the evidence from genetic epidemiologic investigations indicate a significant role of genetics in determining the degree, time course and severity of the atherosclerotic process and of the occurrence of symptomatic CHD. This important role of the genetic component is relevant to preventive strategies offered as tools for reducing the burden of CHD. Research into genetic determinants of both susceptibility to atherosclerosis or clinical manifestation of CHD and individual response to preventive measures should be encouraged.
A parlous state of storm and stress. The life and times of James B. Herrick.
Authors: Ross R S
Published: June 2011

James B. Herrick saw medicine becoming more dependent on science but was unwilling to let the human values of the family doctor vanish. His philosophy was summarized in the phrase, "The true physician must possess a dual personality, the scientific toward disease, the human and humane toward the patient."
Diurnal distribution of ST-segment elevation and related arrhythmias in patients with variant angina: a study by ambulatory ECG monitoring.
Authors: Araki H , Koiwaya Y , Nakagaki O , Nakamura M
Published: June 2011

Twenty-four-hour ambulatory ECG recording was performed in 26 patients with variant angina to evaluate the diurnal distribution of ST-segment elevation in relation to chest pain and the incidence of arrhythmias during the episodes. During a recording period of 52 days, 364 ST-segment elevations of 1 mm or greater were observed and 79% were asymptomatic. ST-segment elevation frequently occurred between 0:00 and 9:00 hours (72%) and most frequently between 5:00 and 6:00 hours (13%). Only a few episodes occurred between 10:00 and 18:00 hours. Premature atrial contractions, premature ventricular contractions (PVCs), ventricular tachycardia (VT) and complete atrioventricular block occurred during 12% of the episodes and were more common during painful episodes (32%) than during painless ones (6%). However, VT and severe forms of PVCs (couplets and bigeminy) appeared eight times during painless episodes and nine times during painful ones. Arrhythmias occurred more frequently when the elevated ST segment started to return or was returning to the control level (n = 38) than when the ST segment was rising (n = 8). The incidence of arrhythmias was lower when the daily frequency of ischemic episodes was high. This study shows that episodes of asymptomatic coronary artery spasm predominantly occur early in the morning as symptomatic episodes; complex dysrhythmias appear during the asymptomatic episodes; arrhythmias occur predominantly during a "reperfusion period;" and more arrhythmias accompany infrequent daily episodes of ischemia than frequent ones.
Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronary artery disease.
Authors: Kern M J , Ganz P , Horowitz J D , Gaspar J , Barry W H , Lorell B H , Grossman W , Mudge G H
Published: June 2011

Although beta-adrenergic blocking agents reduce myocardial oxygen consumption and symptoms of myocardial ischemia in patients with coronary artery disease (CAD), propranolol has been reported to exacerbate coronary artery spasm in some patients with variant angina. To determine whether increased coronary vasomotor tone can be induced by beta-adrenergic blockade, we measured the changes in coronary vascular resistance (CVR) during cold pressor testing (CPT) in 15 patients, nine with severe CAD and six with normal left coronary anatomy, before and after i.v. propranolol (0.1 mg/kg). Coronary blood flow was measured by coronary sinus thermodilution. CVR was calculated as mean arterial pressure divided by coronary sinus blood flow. Heart rate was maintained constant at a paced subanginal rate of 95 +/- 5 beats/min. Before propranolol, CPT induced significant increases in coronary vascular resistance in patients with CAD (15.0 +/- 2.2%, p less than 0.02), but no increase in CVR in the normal patients. After propranolol, the CVR change during CPT was augmented for patients with CAD (29 +/- 6%, p less than 0.01) and for the normal population (9 +/- 5%, NS). The potentiated increase in CVR occurred without significant changes in resting CVR or in the magnitude of the hypertensive response to CPT. We conclude that beta-adrenergic blockade with propranolol can potentiate coronary artery vasoconstriction in some patients with CAD, possibly mediated by unopposed alpha-adrenergic vasomotor tone. These changes may be important in patients in whom intense adrenergic stimulation may increase coronary artery tone and adversely influence the balance between myocardial oxygen supply and demand.
Effect of 12 months of intense exercise training on stroke volume in patients with coronary artery disease.
Authors: Hagberg J M , Ehsani A A , Holloszy J O
Published: June 2011

The purpose of this study was to determine whether 12 months of intense endurance exercise training can induce an increase in left ventricular stroke volume and in stroke work during exercise in patients with coronary artery disease. Eleven male patients were studied. With training, mean maximal oxygen uptake capacity (Vo2max) increased 39%, from 1.85 +/- 0.36 to 2.57 +/- 0.43 l/min. Stroke volume during upright exercise that required 35-65% of Vo2max was 18% higher after training. At the same percentage of Vo2max, mean blood pressure was the same before and after training; as a result, left ventricular stroke work (mean blood pressure X stroke volume) increased 18% (p less than 0.01). These findings suggest that in patients with coronary artery disease, prolonged, intense training induces an increase in stroke volume, and this is a result of cardiac rather than peripheral adaptations.
Electrocardiographic and hemodynamic changes in experimental right ventricular infarction.
Authors: Chou T C , Fowler N O , Gabel M , van der Bel-Kahn J , Feltner E J
Published: June 2011

To investigate the electrocardiographic and hemodynamic changes in isolated right ventricular infarction, 0.25 ml or 0.5 ml of metallic mercury was injected into the right coronary artery of 14 closed-chest dogs. At autopsy, at least 60% of the right ventricle was necrotic in every dog. Hemodynamic observations were made in 11 and electrocardiographic mapping was performed in all 14 dogs. Right atrial pressure rose in 10 and left atrial pressure in nine of the 11 dogs; early right atrial pressure did not exceed left atrial pressure, but late right atrial pressure was greater in four dogs. Although cardiac output and blood pressure fell significantly, circulation was maintained. Twelve of 14 dogs had transient ST-segment elevation in the right precordial leads, and 12 developed right bundle branch block. Abnormal Q waves or R waves of 1 mm or less appeared in the right precordial leads in 13 of the 14 dogs. Since right bundle branch block and abnormal Q waves in the right precordial leads have not been recognized as useful signs in human right ventricular infarction, further investigations are warranted to determine their value in clinical applications.
Right ventricular infarction: role of the moderator band artery in determining infarct size.
Authors: Haupt H M , Hutchins G M , Moore G W
Published: June 2011

We studied 19 patients with proximal right coronary artery occlusions associated with acute myocardial infarcts less than 30 days old. Right ventricular infarct size, determined as a percentage of right ventricular surface area, ranged from 0% to 29%. Correlation of 24 variables measuring infarct size, chamber size and coronary artery disease failed to demonstrate a significant correlation with the extent of right ventricular infarction. However, estimates of the degree of obstruction to potential collateral flow into the right coronary arterial system from the left anterior descending coronary artery, especially through the moderator band artery, showed a significant positive correlation with infarct size (p less than 0.02). Among the five patients with massive (greater than 25%) right ventricular infarction, four had significant (greater than 75%) obstruction of the left anterior descending system, resulting in potentially impaired collateral blood flow; the other patient had normal coronary arteries and embolic occlusion of the proximal right coronary artery with contraction band necrosis. The study suggests that collateral flow to the right ventricular myocardium, especially through the moderator band artery, protects against massive infarction in the presence of proximal right coronary artery occlusion.
Indomethacin-induced scar thinning after experimental myocardial infarction.
Authors: Hammerman H , Kloner R A , Schoen F J , Brown E J , Hale S , Braunwald E
Published: June 2011

We investigated the effect of indomethacin, a widely used nonsteroidal antiinflammatory drug, on the healing of myocardial infarction (MI). Experimental MI was produced in anesthetized, open-chest dogs by occluding the left anterior descending coronary artery. Ten dogs received indomethacin, 10 mg/kg i.v., and 11 received saline, 15 minutes and 3 hours after occlusion. After 6 weeks, the dogs were killed and their hearts were subjected to morphologic and biochemical analysis. The average thickness of the transmural scar and the noninfarcted left ventricular wall was measured at multiple sites in formalin-fixed left ventricular slices and the ratio of the thickness of the transmural scar to the noninfarcted wall determined. The average thickness of the noninfarcted wall was 8.80 +/- 0.19 mm (mean +/- SEM) in the control group and 8.44 +/- 0.26 mm in the indomethacin group (NS). The scar thickness was 7.24 +/- 0.64 mm in the control group and 3.56 +/- 0.40 mm in the indomethacin group (p less than 0.001). The ratio of scar to noninfarcted wall thickness was 0.83 +/- 0.07 in the control group and 0.43 +/- 0.04 in the indomethacin group (p less than 0.001). Scars in treated dogs did not differ from controls either by light microscopic histologic analysis or by analysis of hydroxyproline content per unit weight. We conclude that indomethacin results in marked scar thinning when given early after experimental MI.
Clinical pharmacokinetics and efficacy of amiodarone for refractory tachyarrhythmias.
Authors: Haffajee C I , Love J C , Canada A T , Lesko L J , Asdourian G , Alpert J S
Published: June 2011

Using a high-pressure liquid chromatographic assay, we measured serum amiodarone concentrations serially in 122 patients treated with amiodarone for 1.5-53 months (mean 9.3 months) for control of refractory symptomatic atrial or symptomatic and life-threatening ventricular tachyarrhythmias. The atrial tachyarrhythmias were successfully controlled in 45 of 54 patients (83%) during a mean follow-up of 10.0 months. In the ventricular tachyarrhythmia group, which included 22 survivors of sudden cardiac death, 38 of 50 patients (76%) responded to amiodarone during a mean follow-up of 10.9 months. Although the mean serum amiodarone concentration did not differ between responders and nonresponders, eight responders relapsed when their serum concentration fell below 1.0 mg/l. Side effects resulted in withdrawal of amiodarone in only 10 of 122 patients (9%) despite a 30% overall incidence of side effects. Central nervous system and gastrointestinal side effects became more frequent with serum concentrations greater than 2.5 mg/l, although only central nervous system side effects achieved statistical significance. Absorption and disposition kinetics of a single oral 800-mg dose of amiodarone were studied in eight patients. Serum values were measured for 24 hours in five patients during maintenance therapy, and elimination kinetics after long-term therapy were evaluated in three patients. The tissue concentration of amiodarone was determined in two patients who died during long-term amiodarone therapy and an attempt was made in 14 patients to correlate serum concentrations with daily dosages during maintenance therapy. The pharmacokinetics of oral amiodarone support the practice of using high loading dosages until arrhythmia suppression or apparent steady state is achieved (usually 2-4 weeks), followed by low-dose maintenance therapy (200-600 mg once a day) for treatment of symptomatic atrial and ventricular tachyarrhythmias.
Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations.
Authors: Kuo C S , Munakata K , Reddy C P , Surawicz B
Published: June 2011

The arrhythmogenic role of increased dispersion of repolarization (dispersion) was studied in 23 open-chest dogs using six simultaneously recorded monophasic action potentials (MAPs) from the ventricular surface and programmed ventricular premature stimulation (VPS). Increased dispersion was induced by generalized hypothermia (29 degrees C) and regional warm blood (38-43 degrees C) perfusion through a coronary artery branch. Hypothermia and regional warm blood perfusion increased maximum dispersion from 13 +/- 10 to 111 +/- 16 msec (p less than 0.001), predominantly because of the increased MAP duration difference (10 +/- 15 vs 97 +/- 16 msec, p less than 0.001). The maximal difference between activation times was not significantly changed, but the QRS duration increased from 47 +/- 6 to 52 +/- 7 msec (p less than 0.01). Ventricular arrhythmia did not occur spontaneously but was induced by a single VPS in all 23 dogs during hypothermia and regional warm blood perfusion when dispersion reached a critical magnitude. The critical magnitude of dispersion required to induce ventricular arrhythmia was documented in 16 dogs by stepwise increments or decrements of dispersion. In four dogs, an increase in atrial pacing rate of 24 beats/min prevented induction of ventricular arrhythmia by decreasing dispersion from a critical magnitude of 103 +/- 5 msec to a nonarrhythmogenic value of 86 +/- 9 msec (p less than 0.05). In six dogs, we compared the stimulation site-dependent effects of VPS applied in the region with short and long MAPs. In all dogs, ventricular arrhythmia was inducible only by VPS from the region with a short MAP. Premature impulses from this region propagated more slowly than those from the region with a long MAP. Our results show that the large dispersion of repolarization facilitates the development of a conduction delay necessary to induce sustained arrhythmia by an early premature stimulus applied at the site with a short MAP.
Acceleration of sinus rhythm during slow-rate atrial pacing.
Authors: Haberl R , Steinbeck G , Luderitz B
Published: June 2011

We evaluated the effects of slow-rate atrial pacing on impulse formation of the sinus node in 13 isolated rabbit right atria using the microelectrode technique. After the spread of activation was mapped to determine true sinoatrial conduction time (SACT) (38 +/- 16 msec [+/- SD]), the atrium was paced for eight beats at constant intervals slightly shorter than spontaneous cycle length in steps of 10 msec. In all preparations, slow-rate atrial pacing failed to capture the pacemaker center, but shortened action potential duration because of electrotonic interaction between atrium and sinus node. The resulting acceleration of impulse formation of dominant fibers ceased instantaneously when atrial pacing was terminated. Estimation of SACT by constant pacing 5 beats/min faster than sinus rhythm seriously underestimated the true values (p less than 0.05), because sinus node acceleration prevented capture of dominant pacemaker fibers in 10 of 13 preparations. At pacing rates 10 beats/min faster than sinus rhythm, capture did not occur in eight of 13 experiments; at pacing rates 20 beats/min faster, the pacemaker center was captured in all preparations. This study describes sinus node acceleration as a consistent and hitherto unknown finding during slow-rate stimulation of the atrium. This phenomenon accounts for the failure of the constant atrial pacing technique to determine SACT accurately in man.
Mechanisms of angina relief after nifedipine: a hemodynamic and myocardial metabolic study.
Authors: Emanuelsson H , Holmberg S
Published: June 2011

To elucidate the mechanisms of action of nifedipine in angina pectoris, 14 patients were studied before and after sublingual administration of 10 mg nifedipine. Systemic and coronary hemodynamic and myocardial metabolic measurements were taken at rest and during pacing. At the pacing rate that induced pain in the control situation, no patient experienced angina after nifedipine administration. Lactate production during control turned into extraction after nifedipine administration (p less than .05), and the double product was reduced (p less than .001). Systemic and coronary vascular resistance were reduced by 26% (p less than .001) and 19% (p less than .005), respectively. Systolic blood pressure fell from 160 +/- 29 to 127 +/- 25 mm Hg (p less than .001) and diastolic from 100 +/- 14 to 79 +/- 11 mm Hg (p less than .001). Pulmonary artery diastolic blood pressure fell from 14 +/- 4 to 10 +/- 3 mm Hg (p less than .01). When the pacing rate was further increased after nifedipine administration until pain developed, the double product and the degree of lactate production were the same as during pain before nifedipine was administered. The pacing rate was 131 +/- 12 compared with 119 +/- 13 during control (p less than .001). Both the systolic and diastolic blood pressures were still significantly reduced compared with control pacing values, 131 +/- 26 mm Hg (p less than .01) and 84 +/- 13 mm Hg (p less than .01), respectively. Our data demonstrate that the antianginal efficiency can be partly explained by afterload reduction, which decreases myocardial oxygen consumption. The data also suggest additional mechanisms, possibly an increase in collateral flow, direct dilatation of stenotic parts of epicardial arteries, or a decrease in myocardial back pressure secondary to reduced left ventricular filling pressure.