bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term hemodynamic effects of vasopressin V1-receptor inhibition in chronic right-sided congestive heart failure.
Authors: Stone C K , Liang C S , Imai N , Sakamoto S , Sladek C D , Hood W B
Published: June 2011

Arginine vasopressin is elevated in congestive heart failure. To determine the effect of arginine vasopressin upon systemic hemodynamics and regional blood flows, we administered the specific inhibitor of the vascular action of vasopressin [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)-tyrosine]-arginine vasopressin [d(CH2)5Tyr(Me)AVP] to 15 dogs with chronic right-heart failure produced by tricuspid avulsion and progressive pulmonary artery constriction. The animals exhibited increased plasma arginine vasopressin and norepinephrine levels. Vasopressin inhibition increased cardiac output and left ventricular dP/dt and dP/dt/P, and it decreased total peripheral vascular resistance, whereas mean aortic pressure did not change significantly. Simultaneously, blood flow increased to skeletal muscle, kidneys, skin, and right and left ventricular myocardium. Plasma catecholamines also increased. Pretreatment with propranolol and prazosin abolished the increases in cardiac output and left ventricular function produced by vasopressin inhibition. Pretreatment also led to a decrease in mean aortic pressure after vasopressor inhibition. In contrast, administration of d(CH)2)5Tyr(Me)AVP to 11 sham-operated animals or administration of normal saline to nine sham-operated and eight heart-failure dogs was without effect either in the absence or in the presence of adrenergic receptor blockade. Thus, arginine vasopressin participates in the control of the circulation in right-sided congestive heart failure, with both a direct constrictor action on blood vessels and an indirect action by inhibition of the sympathetic nervous system.
Radiofrequency current directed across the mitral anulus with a bipolar epicardial-endocardial catheter electrode configuration in dogs.
Authors: Jackman W M , Kuck K H , Naccarelli G V , Carmen L , Pitha J
Published: June 2011

This study tested the capability of low-power radiofrequency current delivered through a bipolar "epicardial-endocardial" catheter electrode configuration to produce discrete epicardial left atrial (LA) and left ventricular (LV) necrosis adjacent to the mitral anulus for potential application in ablating left free-wall accessory atrioventricular pathways. In 15 anesthetized, closed-chest dogs, a 6F electrode catheter was inserted via the jugular vein into the coronary sinus (CS). A second catheter was inserted via the femoral artery into the left ventricle and positioned beneath the mitral valve, high against the anulus, and directly opposite the CS electrode. The LV tip electrode was positioned to record the largest LA potential to ensure proximity to the anulus. Thirty-four sites were tested (five anterior, 14 lateral, and 15 posterior). Radiofrequency current (continuous wave, 625 kHz) was delivered between the CS and LV electrodes at 37-55 V (median, 41 V) for 4-60 seconds (median, 20 seconds). Current ranged from 0.10 to 0.35 A (median, 0.18 A), resulting in power ranging from 4.3 to 19.2 W (median, 7.3 W) and total energy of 51-446 J (median, 152 J). Dogs were sacrificed 2-9 days later. The CS was grossly intact in all dogs and thrombosed in one dog. The circumflex artery was grossly normal in all dogs. Necrosis of a small segment of the arterial wall was found microscopically in one dog. Lesions were identified at 30 of the 34 sites. Twenty-two (73%) of the 30 lesions consisted of a cylindrical-shaped area of necrosis extending between the anulus and CS with diameter ranging from 2.1 to 15.0 mm (median, 4.0 mm). Atrial and ventricular epicardial necrosis extended 0-7.0 mm (median, 2.5 mm) and 0-6.8 mm (median, 2.6 mm) beyond the anulus, respectively. At the remaining eight (27%) sites, little or no epicardial injury occurred, possibly because of downward displacement of LV electrode (four sites) or positioning of LV electrode within a trabecular recess (four sites). We conclude that 1) radiofrequency current delivered between CS and LV produced, at 22 (65%) of 34 sites, LA and LV necrosis adjacent to the anulus without rupture of the CS and that 2) large, sharp LA potentials help identify an optimal anular location of LV electrode. This technique may have clinical usefulness for ablating left free-wall accessory atrioventricular connections.
Effects of load alteration and coronary perfusion pressure on regional end-systolic relations.
Authors: Miller W P , Flygenring B P , Nellis S H
Published: June 2011

Left ventricular end-systolic pressure-wall thickness and pressure-segment length relations have been used to assess regional myocardial contractility. The purpose of these studies was to determine whether the method of afterload alteration, coronary perfusion pressure, and the definition of end systole affected regional end-systolic relations. In paced open-chest pig hearts (n = 10), left ventricular pressure, wall thickness, and segment length were measured during vena caval occlusions. First, regional end-systolic relations were obtained before and after an increase in afterload with intravenous phenylephrine. This comparison was performed with the coronary circulation intact (closed loop) and with coronary perfusion pressure controlled extracorporeally (open loop). Second, with the open-loop preparation, the independent effect of a range of coronary perfusion pressures (45-155 mm Hg) on end-systolic relations was assessed. In both procedures, end systole was defined by the maximal isochronal slope, termed regional Emax, and by the maximal ratio of left ventricular pressure to regional dimension, termed Ees. In the first procedure, the slope and x-axis intercept of regional Emax were unchanged with phenylephrine. In contrast, the slope of Ees decreased with phenylephrine, consistent with a decrease in contractility. The extrapolated x-axis intercept of Ees shifted in a direction consistent with an increase in contractility. In the second procedure, increases in coronary perfusion pressure did not affect regional Emax but increased the slope of Ees. A decrease in the coronary perfusion pressure, particularly with ischemia, shifted the x-axis intercepts of both Emax and Ees in a direction consistent with a decrease in contractility. Thus, regional end-systolic relations in intact hearts are dependent on the method of afterload alteration and the coronary perfusion pressure. Furthermore, Emax differs from Ees, so the assessment of regional relations depends on how end systole is defined.
Early noninvasive detection of successful reperfusion in patients with acute myocardial infarction.
Authors: Ellis A K , Little T , Masud A R , Liberman H A , Morris D C , Klocke F J
Published: June 2011

Myoglobin (Mb) is a protein that enters rapidly and is rapidly cleared from plasma after coronary reperfusion. We sought to determine the accuracy with which a rapid rise in plasma [Mb] could predict successful coronary artery reopening in patients undergoing coronary arteriography in conjunction with attempted reperfusion in acute myocardial infarction. In 42 patients, plasma Mb levels were measured before and for at least 4 hours after attempted reperfusion. Thirty-five patients were successfully reperfused. In each, the plasma Mb level rose rapidly with peak [Mb] occurring at 111 +/- 8.1 (+/- SEM) minutes after application of therapy. In contrast, Mb levels rose more slowly in the seven patients who were not reperfused, with peak [Mb] occurring 360 +/- 61.4 minutes after attempted reperfusion. T25-100 (the time required for [Mb] to rise from 25% to 100% of peak value) was shorter in patients successfully reperfused (71 +/- 7.9 minutes) and longer (341 +/- 35.3 minutes) in patients in whom therapy was unsuccessful. A rapid rise in [Mb] after successful reperfusion was also evident by a more than 4.6-fold rise in [Mb] over the first 2 hours after reperfusion in all but five patients; in contrast, [Mb] rose by less than 4.6-fold over this same interval in every patient not successfully reperfused (sensitivity, 85%; specificity, 100%; predictive accuracy, 88%). We conclude that a rapid rise in plasma Mb level over the initial 2 hours after attempted reperfusion in acute myocardial infarction provides a useful index of successful reperfusion.
Fate of left ventricular thrombi in patients with remote myocardial infarction or idiopathic cardiomyopathy.
Authors: Stratton J R , Nemanich J W , Johannessen K A , Resnick A D
Published: June 2011

Although left ventricular thrombi that form acutely after myocardial infarction frequently resolve spontaneously or with anticoagulant therapy, the fate of left ventricular thrombi in patients with remote myocardial infarction or with idiopathic cardiomyopathy remains unknown. To determine the natural history of such chronic left ventricular thrombi, we performed serial echocardiograms on 51 patients with remote myocardial infarction (greater than or equal to 3 months; mean, 31 +/- 41 months) and on nine patients with idiopathic dilated cardiomyopathy. Mean follow-up was 24 +/- 22 months during which 3.5 +/- 1.4 echocardiograms were obtained. Studies were interpreted by blinded observers, and an increase or decrease of more than 5 mm in maximal thrombus thickness was defined as significant. Among all 60 patients left ventricular thrombi were unchanged in 24 (40%), completely resolved in 24 (40%), decreased in size in four (7%), increased in size in five (8%), and decreased and then increased in size in three (5%). Results in patients with remote infarction and idiopathic cardiomyopathy were similar. Warfarin therapy, which was at the discretion of the primary physician, was associated with a higher prevalence of thrombus resolution compared with no therapy (59% vs. 29%, p = 0.02). Definite systemic emboli occurred in seven patients (12%), all at times while they were not anticoagulated. Among the 48 thrombi that were present on two or more echocardiograms, changes in thrombus shape (classified as protruding or flat) occurred in only 16%, and changes in thrombus movement (classified as mobile or immobile) occurred in only 10%.(ABSTRACT TRUNCATED AT 250 WORDS)
Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury.
Authors: Crawford M H , Grover F L , Kolb W P , McMahan C A , O'Rourke R A , McManus L M , Pinckard R N
Published: June 2011

Complement depletion with cobra venom factor (CVF) before coronary artery ligation has been previously shown to reduce subsequent ischemic myocardial tissue injury in the baboon; however, whether complement depletion after the initiation of acute myocardial ischemia affords similar myocardial preservation is not known. Both complement depletion with CVF or the administration of certain nonsteroidal anti-inflammatory drugs, including ibuprofen, are thought to decrease myocardial infarct size by reducing polymorphonuclear leukocytic (PMN) infiltration; nevertheless, complement activation also could alter tissue injury by PMN-independent actions. Thus, the relative effects of CVF administered after coronary artery ligation on the subsequent development of myocardial tissue injury were assessed in a baboon myocardial infarction model. The animals were randomized into three treatment groups (n = 6): either CVF (125 units/kg) or saline was given 30 minutes after coronary artery ligation, and ibuprofen (12.5 mg/kg) was administered 30 minutes and 4 hours after ligation. The extent of ischemic myocardial injury was assessed 24 hours later. Relative to saline-treated baboons, both CVF and ibuprofen reduced PMN infiltration (36 +/- 4 vs. 24 +/- 4 and 24 +/- 4 PMN/mm2, respectively; mean +/- SEM) and histological evidence of transmural myocardial infarction (100% vs. 47% and 53%, respectively) in electrocardiographically designated, expected infarct sites. In both saline- and ibuprofen-treated animals, there was extensive localization of C4, C3, and C5 in all infarct sites; in contrast, there was only C4 localization in the CVF-treated baboons. When expected infarct sites were assessed for creatine kinase content as an indicator of tissue injury, there was significantly less epicardial and endocardial creatine kinase depletion in the CVF-treated animals (31.7 +/- 5.6% and 39.3 +/- 4.8%) than in the saline-treated animals (54.1 +/- 5.4% and 59.0 +/- 4.7%; p = 0.012 and 0.011, respectively). The percent creatine kinase depletion in the ibuprofen-treated animals was intermediate between the two other groups. These results suggest that depletion of complement after coronary ligation has beneficial effects in reducing tissue injury that cannot be explained solely on the basis of reducing PMN infiltration into the ischemic myocardium.
Noninvasive quantitation of regional myocardial oxygen consumption in vivo with [1-11C]acetate and dynamic positron emission tomography.
Authors: Buxton D B , Nienaber C A , Luxen A , Ratib O , Hansen H , Phelps M E , Schelbert H R
Published: June 2011

The usefulness of [1-11C]acetate as a tracer of overall myocardial oxidative metabolism for use with positron emission tomography has been investigated in 12 closed-chest dogs. Myocardial 11C activity clearance kinetics after intravenous administration of [1-11C]acetate in dogs have been determined noninvasively by positron emission tomography. Biexponential fitting of regional myocardial 11C time-activity curves was performed to give clearance half-times and fractional distribution. The rate constant k1 for the early rapid phase of 11C activity clearance was found to correlate linearly with myocardial oxygen consumption (y = 0.0156x + 0.039; SEE = 0.023; r = 0.95). k1 was approximately 7% lower in septal sectors compared with the left ventricular free wall, suggesting that regional oxygen consumption in the septum was lower; a concomitant regional attenuation of blood flow in the septum relative to the left ventricular free wall was also observed. In dogs using carbohydrates as the predominant fuel, k1 oxygen consumption was somewhat more than in dogs using predominantly free fatty acids (0.021 +/- 0.002 compared with 0.018 +/- 0.002, p less than 0.01), indicating that increased carbohydrate consumption is associated with a small increase in k1 at constant oxygen consumption. It is concluded that measurement of myocardial [1-11C]acetate kinetics allows noninvasive determination of cardiac oxygen consumption by positron emission tomography and that the technique is relatively insensitive to myocardial fuel selection.
Intensive combination drug therapy of familial hypercholesterolemia with lovastatin, probucol, and colestipol hydrochloride.
Authors: Witztum J L , Simmons D , Steinberg D , Beltz W F , Weinreb R , Young S G , Lester P , Kelly N , Juliano J
Published: June 2011

Patients with familial hypercholesterolemia (FH) have had a life-long sustained elevation of low-density lipoprotein (LDL) cholesterol levels. Consequently, there is a need to maximally lower their elevated levels, and this usually requires lowering LDL levels more than 50%. Because no single hypolipidemic drug will consistently produce such degrees of lowering, combination drug therapy with two or even three agents is required to produce the desired degree of cholesterol lowering. A prospective trial was designed to determine if combination therapy using three hypolipidemic agents could effectively lower LDL levels in 17 severely affected FH subjects. Colestipol hydrochloride (10 g b.i.d.), probucol (500 mg b.i.d.), and lovastatin (20 or 40 mg b.i.d.) were given to each patient, in varying combinations, over a 25-month period. Lovastatin (40 mg/day) uniformly lowered LDL levels 36%. Probucol lowered LDL only 14% and in a variable manner. The combination of lovastatin and probucol lowered LDL no better than lovastatin alone. Lovastatin plus colestipol lowered LDL 52%; probucol added as a third agent produced no further lowering. Lovastatin (80 mg/day) plus colestipol lowered LDL 56%. Lovastatin increased high-density lipoprotein (HDL) cholesterol levels 6%, whereas probucol decreased HDL 29%. In all patients there was an effective lowering of LDL levels, ranging from 40% to 70%. Thus, lovastatin plus colestipol is an effective hypolipidemic regimen for producing marked decreases in LDL levels in FH subjects. The addition of probucol as a third hypolipidemic agent adds little to the therapeutic regimen as measured by lowering of LDL levels.
Influence of contractile state on curvilinearity of in situ end-systolic pressure-volume relations.
Authors: Kass D A , Beyar R , Lankford E , Heard M , Maughan W L , Sagawa K
Published: June 2011

Although in situ end-systolic pressure-volume relations (ESPVRs) are approximately linear throughout a limited load range, they often yield seemingly "negative" volume axis intercepts (V0) and V0 shifts with inotropic interventions. We tested whether or not these findings could stem from in situ ESPVR nonlinearity, and we examined the physiologic meaning and limitations of linearized ESPVR variables frequently used for assessing contractile state. Continuous left ventricular pressures and volumes were obtained by micromanometer and conductance (volume) catheters in six open-chest dogs. Left ventricular loading was varied throughout a wide range by rapid left atrial hemorrhage into a reservoir. Propranolol and verapamil were administered to reduce inotropic state, with heart rate maintained by atrioventricular sequential pacing. ESPVRs were fit to nonlinear [Pes = a(Ves-V'0)2 + b(Ves-V'0)] and linear (Pes = Ees (Ves-V0)] models. Contractile state was assessed by the slope of the ESPVR at V'0 (b, of nonlinear model) and by two other ESPVR model-independent measures: the slope of the dP/dtmax and end-diastolic volume relation, and the slope of the stroke work and end-diastolic volume relation. ESPVR was frequently curvilinear, and a significant correlation existed between the extent of nonlinearity (a) and contractile state. Volume intercepts derived from linear fits to the high load ESPVR range were mostly negative and were dependent on changes in Ees. V0 estimates derived from the low load portion were positive and relatively insensitive to Ees. Thus, in situ ESPVR displays contractility-dependent curvilinearity. The contractility range throughout which ESPVRs are essentially linear is typical for isolated hearts, but the range represents low values for in situ ventricles. Despite curvilinearity, Ees determined in situ throughout limited load ranges can accurately assess inotropic state; however, comparisons between ESPVRs should consider potential nonlinearity, and if possible, they should be made within similar end-systolic pressure ranges.
Flow-mediated and reflex changes in large peripheral artery tone in humans.
Authors: Anderson E A , Mark A L
Published: June 2011

Studies of peripheral blood vessels in humans have focused primarily on regulation of blood flow and vascular resistance, which are thought to reflect small vessel caliber. Recent studies in animals have identified flow-mediated and neurogenic changes in large artery diameter. This study tested for flow-mediated dilatation and reflex constriction of the brachial artery in humans. A dual-crystal pulsed Doppler system was used to measure brachial artery diameter and blood flow proximal to the antecubital fossa. To test for flow-mediated dilatation, flow through the brachial artery was altered by an occluding cuff placed on the forearm distal to the site of brachial artery flow and diameter measurement. Control blood flow was 123 +/- 20 ml/min, and brachial artery diameter was 4.74 +/- 0.17 mm (mean +/- SEM). By inflating the distal occluding cuff (distal circulatory arrest), flow was reduced through the brachial artery to 21 +/- 5 ml/min (p less than 0.005), and brachial artery diameter was reduced to 4.35 +/- 0.20 mm (p less than 0.001). By deflating the distal occluding cuff after 10 minutes (reactive hyperemia), brachial artery flow was increased to 358 +/- 55 ml/min (p less than 0.001), and diameter was increased to 5.6 +/- 0.19 mm (p less than 0.001). These interventions did not change systemic arterial pressure and, as measured in three subjects, caused only small changes in local brachial artery distending pressure. Thus, both increased and decreased brachial artery blood flow produced significant changes in brachial artery diameter without altering arterial distending pressure. These data provide evidence for flow-mediated dilatation in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
A decision scheme for coronary angiography after acute myocardial infarction.
Authors: Ross J , Gilpin E A , Madsen E B , Henning H , Nicod P , Dittrich H , Engler R , Rittelmeyer J , Smith S C , Viquerat C
Published: June 2011

It is important to select patients in the convalescent phase of acute myocardial infarction in whom knowledge of coronary anatomy may identify those potentially suitable for intervention aimed at improving prognosis. However, differing guidelines have been proposed, and by applying some of these guidelines to our large database of patients after acute myocardial infarction, several problem areas were identified. These include lack of considering patients with resting ischemia beyond day 5 of hospitalization, management of patients with reduced ventricular function or patients not exercise tested, and the role of coronary angiography in the elderly. Based on this experience and further analysis in 1,848 patients surviving beyond day 5 of hospitalization, a modified decision scheme for coronary angiography was developed and then tested in a second population (n = 780). In the new scheme, patients over 75 years of age are considered individually. Those under 75 years of age with severe resting ischemia in the hospital at any time beyond the first 24 hours (18% mortality between day 6 and year 1), and hospital survivors with a history of previous myocardial infarction and clinical or radiographic signs of left ventricular failure in the hospital (25% 1-year mortality after discharge), are recommended for coronary angiography. Among the remaining patients, some will perform an exercise test, and those with an ischemic response or poor workload (11% 1-year mortality) are also assigned to coronary angiography. When an exercise test is not performed, a resting radionuclide left ventricular ejection fraction is recommended, and coronary angiography is considered if the value lies between 0.20 and 0.44 (12% 1-year mortality). This relatively simple scheme does not make general recommendations in the elderly, considers patients with in-hospital left ventricular failure or reduced left ventricular function or both, and approaches the problem of patients who do not perform an exercise test. This general approach would avoid early coronary angiography in patients with an average 1-year mortality risk after discharge of 3% and recommend coronary angiography in those at increased risk (average mortality rate, 16%) who make up about 55% of this population under 75 years of age.
Exercise training in patients with chronic heart failure delays ventilatory anaerobic threshold and improves submaximal exercise performance.
Authors: Sullivan M J , Higginbotham M B , Cobb F R
Published: June 2011

We have recently demonstrated that exercise training can induce important hemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examines the accompanying changes in submaximal exercise performance and the ventilatory response to exercise in these patients. Before and after 16-24 weeks of exercise training, subjects underwent two symptom-limited bicycle exercise tests, one with an incremental graded workload, and one with a constant workload that represented 79 +/- 11% of the pretraining peak oxygen consumption. Breath-by-breath expired gas analysis was performed continuously during each test, and central hemodynamic, leg blood flow, and blood lactate measurements were obtained during the incremental protocol. The ventilatory anaerobic threshold was determined during the incremental exercise study from coplotted breath-by-breath ventilatory data with standard criteria by observers who were unaware of patient identity or training status. As previously reported, exercise training increased peak oxygen consumption by 23% from 16.8 +/- 3.8 to 20.6 +/- 4.7 ml/kg/min and reduced blood lactate levels during submaximal exercise. The training-induced decrease in lactate accumulation was accompanied by a decrease in carbon dioxide production, respiratory exchange ratio, and ventilation during submaximal exercise. The ventilatory anaerobic threshold was delayed from 284 +/- 43 to 352 +/- 91 seconds of exercise (p = 0.02), and it occurred at an increased oxygen consumption (10.1 +/- 1.2 vs. 12.1 +/- 2.6 ml/kg/min, p = 0.01). Exercise duration during the constant workload protocol increased from 938 +/- 410 to 1,429 +/- 691 seconds (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Mitral prosthesis malfunction. Comparative Doppler echocardiographic studies of mitral prostheses before and after replacement.
Authors: Nellessen U , Masuyama T , Appleton C P , Tye T , Popp R L
Published: June 2011

To assess the influence of mitral prosthesis malfunction on various Doppler echocardiographic indexes, we studied the changes in the peak mitral flow velocity during early diastolic filling phase (Vmax), the mean transprosthesis pressure drop from the simplified Bernoulli equation, the mitral valve area by the pressure half-time method, and the left ventricular isovolumic relaxation time in 15 patients before and after replacement of the malfunctioning mitral prosthesis using continuous wave Doppler echocardiography. Examination of the 15 replaced prostheses revealed a torn or perforated leaflet in 12 valves and a sewing ring dehiscence in one valve. Additional restricted leaflet motion (classified as mild obstruction) was seen in three of these 13 valves. In the remaining two valves, severe prosthesis obstruction was noted. Changes in the Doppler indexes between the preoperative and postoperative study were present in all patients regarding Vmax (mean, 2.2 +/- 0.3 versus 1.6 +/- 0.2 m/sec; p less than 0.001), mean gradient (mean, 9 +/- 5 versus 5 +/- 0.8 mm Hg; p less than 0.001), and isovolumic relaxation time (mean, 47 +/- 12 msec versus 80 +/- 13 msec; p less than 0.001). The mean mitral valve area remained virtually unchanged (2.3 +/- 0.9 versus 2.6 +/- 0.3 cm2; p = NS) but increased postoperatively in each patient with preoperative mild or severe prosthesis obstruction without concomitant aortic regurgitation. Our conclusion is that the peak mitral flow velocity, the mean gradient, and the isovolumic relaxation time are useful parameters in the differentiation of normal and abnormal mitral prosthesis function but may not define the underlying lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
A new mechanism for atrioventricular nodal gap-vagal modulation of conduction.
Authors: Mazgalev T , Dreifus L S , Michelson E L
Published: June 2011

The well-known paradoxic behavior of atrioventricular conduction, the so-called gap phenomenon, that occurs when impulses within a certain range of coupling intervals are blocked while impulses with shorter coupling intervals are conducted is attributed to differences in properties of refractoriness in neighboring regions of the conduction system. In contrast, in the present study a model was developed showing a similar phenomenon, dependent on different electrophysiologic mechanisms and localized within the atrioventricular node in an isolated rabbit heart tissue preparation (n = 11). The hearts were paced at cycle length of 400-500 msec, and atrioventricular nodal conduction times (A2H2) were measured versus atrial extrastimulus (A1A2) coupling intervals by standard extrastimulus techniques. Postganglionic vagal stimulation was applied in the atrioventricular node as short bursts of subthreshold (for myocardium) stimuli with duration of 50-150 msec, amplitude of 20-800 microA, and absolute phase (delay after A1) of 0-500 msec. Vagal bursts with appropriate parameters consistently produced bimodal conduction curves. Initially, gradual shortening of the A1A2 coupling interval was associated with an increasing A2H2, with an accentuated increase (or even atrioventricular block) within an intermediate A1A2 range. However, further shortening of the A1A2 coupling interval produced a decrease in A2H2, which subsequently was followed by a block at the effective refractory period. Microelectrode recordings indicated that this characteristic bimodal pattern of conduction curves, demonstrating a gap, reflected transient vagally induced hyperpolarization in the N region of the node. In those instances where conduction block occurred and gap was manifest, the most marked hyperpolarization coincided with the time of arrival of midcycle premature extrastimuli, whereas the conduction of extrastimuli with either more or less prematurity was under less-marked vagal influence. Thus, this study demonstrates a new electrophysiologic mechanism producing anomalous conduction curves and the gap phenomenon within the atrioventricular node based on vagal-induced nonuniform recovery of diastolic excitability.
Preload-induced curvilinearity of left ventricular end-systolic pressure-volume relations. Effects on derived indexes in closed-chest dogs.
Authors: Su J B , Crozatier B
Published: June 2011

End-systolic pressure-volume relations (ESPVRs) were analyzed in 10 closed-chest autonomically blocked dogs before and after volume loading that restored end-diastolic volume to its value measured in the control conscious state. Dogs had been previously instrumented with a left ventricular pressure micromanometer and ultrasonic crystals for measurements of major, anteroposterior, and septum-free wall diameters. Left ventricular volume was calculated with an ellipsoidal model in the left ventricular cavity. ESPVRs obtained during caval occlusion after volume loading were curvilinear as shown by the division of the relation into two parts. The initial part of the relation had a significantly smaller ESPVR slope (Ees, 12.0 +/- 1.8 mm Hg/ml) and ESPVR volume-axis intercept (Vd, - 3.5 +/- 0.8 ml) than the final part of the relation (19.5 +/- 3.1 mm Hg/ml and 0.0 +/- 0.6 ml, respectively, p less than 0.01). The end-diastolic volume-peak dP/dt relation showed a similar curvilinearity when end-diastolic volumes were larger than 1.5-1.7 times the minimal end-diastolic volume reached during caval occlusion. ESPVRs were not different during aortic constriction and caval occlusion when end-diastolic volume was small. In contrast, with large end-diastolic volumes, Ees and Vd were significantly smaller during caval occlusion than during aortic constriction. The final part of ESPVR (with small end-diastolic volume) had the same slope and intercept as that during aortic constriction. We conclude that preload produces a curvilinearity of ESPVR that significantly modifies derived indexes when the range of preload changes is large.
Instrumentation and practice standards for electrocardiographic monitoring in special care units. A report for health professionals by a Task Force of the Council on Clinical Cardiology, American Heart Association.
Authors: Mirvis D M , Berson A S , Goldberger A L , Green L S , Heger J J , Hinohara T , Insel J , Krucoff M W , Moncrief A , Selvester R H
Published: June 2011

The proposed recommendations for continuous electrocardiographic monitoring systems represent goals for future development. Description of a technique in the report does not constitute an endorsement of its clinical use. Lead systems for ECG monitoring must adequately sense the cardiac electrical field and the leads should be standardized. Future monitors should be capable of simultaneously displaying and analyzing multiple leads. Recommendations for electrode placement and position of patient are made. Important parameters in each category of standards for instrumentation published in 1983 in the American National Standard for Cardiac Monitors, Heart Rate Meters, and Alarms are listed. Selected procedures proposed by the Association for the Advancement of Medical Instrumentation to inform users of minimally acceptable accuracy of computerized systems in a standardized manner are presented. Emphasis is placed on the importance of nursing and medical staff capabilities. Personnel qualifications and training as well as systems to assure and maintain quality of immediate ECG diagnosis are highlighted.
Office evaluation of hypertension. A statement for health professionals by a writing group of the Council for High Blood Pressure Research, American Heart Association.
Authors: Gifford R W , Kirkendall W , O'Connor D T , Weidman W
Published: June 2011

The ultimate purpose of office evaluation of the hypertensive patient is to provide optimal management of blood pressure and associated risk factors. The workup includes a valid estimate of average blood pressure, including home blood pressure measurements, assessment of the degree of target organ damage, and identification of other risk factors, including family history. The history and physical examination should be directed to the principal target organs, including the optic fundi, central nervous system, heart, and kidneys. Laboratory evaluation should include urinalysis, ECG, and determinations of blood hemoglobin/hematocrit, creatinine, potassium, glucose, and cholesterol, including HDL fraction. This information will alert the physician to the possibility of curable forms of hypertension such as coarctation of the aorta, pheochromocytoma, primary aldosteronism, and renovascular hypertension. The office evaluation is also concerned with estimating prognosis and extent of organic damage, which is essential in planning management. The nurse or trained allied health professional should be used to the fullest possible extent both in evaluation and management of hypertensive patients.
Left ventricular myocardial structure in aortic valve disease before, intermediate, and late after aortic valve replacement.
Authors: Krayenbuehl H P , Hess O M , Monrad E S , Schneider J , Mall G , Turina M
Published: June 2011

Left ventricular biplane cineangiography, micromanometry, and endomyocardial biopsies were performed in 27 patients with aortic stenosis (AS) and in 17 patients with aortic insufficiency (AI). Twenty-three patients with AS and 15 with AI were restudied at an intermediate time (18 months after successful valve replacement), and nine patients with AS and six with AI were restudied late (70 and 62 months after surgery). Biopsy samples were evaluated for muscle fiber diameter, percent interstitial fibrosis, and volume fraction of myofibrils. In control biopsy samples obtained from five donor hearts at transplantation, these morphometric variables averaged 21.2 microns, 7.0%, and 57.2%, respectively. After surgery, mass determined by cineangiography decreased from 186 to 115 and 94 g/m2 in patients with AS and from 201 to 131 and 93 g/m2 in patients with AI. At the three studies, muscle fiber diameter was 30.9, 28.0, and 28.7 microns in patients with AS and was 31.4, 27.6, and 26.4 microns in patients with AI. Percent interstitial fibrosis was 18.2, 25.8, and 13.7% in patients with AS and was 20.4, 23.7, and 19.2% in patients with AI. Left ventricular fibrous content decreased from 34.2 to 29.8 and to 12.7 g/m2 in patients with AS and from 42.1 to 28.9 and to 18.9 g/m2 in patients with AI. Volume fraction of myofibrils was 57.7, 56.8, and 49.0% in patients with AS and was 56.8, 56.6 and 48.8% in patients with AI. Thus, the decrease of muscle mass determined by cineangiography at the intermediate time after valve replacement is mediated by regression of myocardial cellular hypertrophy in patients with AS and AI and in addition by a decrease of fibrous content in patients with AI. Late after surgery, left ventricular fibrous content also decreases in patients with AS. This late decrease associated with minor changes of end-diastolic volume may be important for improvement of increased diastolic myocardial stiffness. Even 6-7 years after valve replacement, incomplete regression of structural abnormalities of left ventricular hypertrophy still exists compared with the normal myocardium. The residually increased relative interstitial fibrosis and the small late postoperative decrease of volume fraction of myofibrils, associated with a prosthesis-related slight left ventricular pressure increase, are at the origin of a persistent systolic overload at the myofibrillar level.
Sudden coronary death in the United States: 1980-1985.
Authors: Gillum R F
Published: June 2011

To describe patterns of an indicator of sudden coronary death, data from the National Center for Health Statistics were examined for deaths occurring out of hospital and in the emergency room (OH/ER) from 1980 to 1985 in 40 states. In 1985, 56% of ischemic heart disease deaths occurred OH/ER among persons aged 35-74 years. The percentage occurring OH/ER declined with age, was higher in men than women, and higher in blacks than whites. At age 55-64, 61% of ischemic heart disease deaths in white and 66% in black men occurred OH/ER. Between 1980 and 1985, age-adjusted death rates in white men aged 35-74 years declined 19% for OH/ER and 18% for in-hospital ischemic heart disease deaths. The percentage of deaths in ER increased. The decline in deaths occurring OH/ER accounted for 61% of the total absolute decline in ischemic heart disease death rate in white men, 55% in white women, and about 70% in nonwhites. The decline in rates of death OH/ER should encourage further efforts at preventing coronary heart disease and improving emergency medical services.
Assessment of coronary artery disease severity by positron emission tomography. Comparison with quantitative arteriography in 193 patients.
Authors: Demer L L , Gould K L , Goldstein R A , Kirkeeide R L , Mullani N A , Smalling R W , Nishikawa A , Merhige M E
Published: June 2011

To assess the accuracy of positron emission tomography (PET) for evaluation of coronary artery disease (CAD), cardiac PET perfusion images were obtained at rest and with dipyridamole-handgrip stress in 193 patients undergoing coronary arteriography. PET images were reviewed by two independent readers blinded to clinical data. Subjective defect severity scores were assigned to each myocardial region on a 0 (normal) to 5 (severe) scale. Results were compared with arteriographic stenosis severity expressed as stenosis flow reserve (SFR), with continuous values ranging from 0 (total occlusion) to 5 (normal), calculated from quantitative arteriographic dimensions using automated detection of the vessel borders. There were 115 patients with significant CAD (SFR less than 3), 37 patients with mild CAD (3 less than or equal to SFR less than 4), and 41 patients with essentially normal coronaries (SFR greater than or equal to 4). With increasingly severe impairment of stenosis flow reserve, subjective PET defect severity increased. Despite wide scatter, a PET score of 2 or more was highly predictive of significant flow reserve impairment (SFR less than 3). For each patient, the score of the most severe PET defect correlated with the SFR of that patient's most severe stenosis (rs = 0.77 +/- 0.06). For each of 243 stenoses, PET defect score correlated with the SFR of the corresponding artery (rs = 0.63 +/- 0.08). PET defect location closely matched the region supplied by the diseased artery, and readers agreed whether the most severe PET defect was less than or more than 2 for 89% of patients.
Reperfusion alters the relation between blood flow and the remaining myocardial infarction.
Authors: Chu A , Cobb F R
Published: June 2011

This study evaluated whether or not reperfusion of ischemic myocardium 2 hours after occlusion alters the basic relation between myocardial blood flow and infarction occurring during permanent occlusion. Awake mongrel dogs chronically instrumented with proximal circumflex coronary occluders were subjected to permanent occlusion (group A, n = 10) or occlusion followed by reperfusion 2 hours later (group B, n = 11). Myocardial blood flow was quantified with radioactive microsphere injections before, 6 hours after occlusion (group A), immediately before release, and 4 hours after reperfusion (group B). Three days later, the dogs were killed, and the heart was sectioned systematically into approximately 80 1-2-g circumferential and transmural samples for radioactive counting and histologic infarct quantification. Epimyocardial and endomyocardial samples from the permanent occlusion group (A) and the reperfused group (B) were separated by infarct range and related to regional myocardial blood flow measurements. In groups A and B, regional myocardial blood flow in endomyocardial and epimyocardial layers were inversely related to the extent of infarction. For given degrees of infarction, myocardial blood flow was significantly higher (greater than twofold) in the reperfused group. Myocardial samples with extensive infarction (51-75%) showed only mild (20-30%) reductions in blood flow when compared with nonischemic regions in the reperfused group. Thus, although early reperfusion may salvage ischemic myocardium, these studies showed that reperfusion causes a new relation between blood flow to the ischemic region and eventual histologic infarct size. When myocardial blood flow is used as an index of myocardial salvage after reperfusion, the basic relation obtained from permanent occlusion studies substantially overestimates the extent of myocardial salvage and underestimates the degree of remaining infarction.
Rate-related electrophysiologic effects of long-term administration of amiodarone on canine ventricular myocardium in vivo.
Authors: Anderson K P , Walker R , Dustman T , Lux R L , Ershler P R , Kates R E , Urie P M
Published: June 2011

The electrophysiologic effects of amiodarone were examined in 13 dogs that received 30 g amiodarone orally during 3 weeks and compared with 13 control dogs that did not receive amiodarone. Longitudinal and transverse epicardial conduction velocities were estimated with a square array of 64 closely spaced electrodes and a computer-assisted acquisition and analysis system. Amiodarone caused a rate-dependent decrease in conduction velocity with a slightly greater effect in the longitudinal direction of propagation. Rate-related depression of conduction velocity developed rapidly after abrupt shortening of the pacing cycle length; 67% of the change occurred between the first two beats of the rapid train, and little change occurred after the 10th beat. Recovery from use-dependent depression of conduction velocity was exponential with a mean time constant of 447 +/- 172 msec in the longitudinal direction and 452 +/- 265 msec in the transverse direction. Repolarization intervals, defined as the interval between the activation time and the repolarization time in the unipolar electrograms, correlated highly with refractory period determinations in the absence and presence of amiodarone at each cycle length tested. The increase in repolarization intervals and refractory periods resulting from amiodarone treatment did not vary with cycle length. Amiodarone treatment also resulted in a significant rate-related reduction in systolic blood pressure. The systolic blood pressure in the group that received amiodarone decreased by a mean of 50 +/- 23% between steady-state pacing cycle lengths of 1,000 and 200 msec, whereas the corresponding decrease in the control group was 21 +/- 32% (p less than 0.05). Plasma and myocardial amiodarone and desethylamiodarone levels were comparable to those observed clinically. We conclude that long-term amiodarone administration causes rate-dependent reductions in conduction velocity and blood pressure and causes rate-independent increases in repolarization intervals.
Beta-adrenergic receptor number and adenylate cyclase function in denervated transplanted and cardiomyopathic human hearts.
Authors: Denniss A R , Marsh J D , Quigg R J , Gordon J B , Colucci W S
Published: June 2011

To test the hypothesis that there is up-regulation of beta-adrenergic receptor density or supersensitivity of beta-adrenergic receptor-stimulated adenylate cyclase in the denervated transplanted human heart, we studied myocardium from transplanted, normal, and failing hearts. Myocardium was obtained from 10 patients 9 +/- 3 months after cardiac transplantation, from 10 patients without cardiac disease, and from eight patients with symptomatic congestive heart failure due to idiopathic cardiomyopathy. beta-Adrenergic receptor density in transplanted myocardium (15 +/- 3 fmol/mg protein, 1.20 +/- 0.14 fmol/mg DNA) was not different from that in normal myocardium (22 +/- 3 fmol/mg protein, 1.46 +/- 0.13 fmol/mg DNA; p = NS for both). In myocardium from cardiomyopathic hearts, beta-adrenergic receptor density was markedly reduced (8 +/- 2 fmol/mg protein, 0.84 +/- 0.13 fmol/mg DNA; p less than 0.05 and p less than 0.01 vs. normal myocardium, respectively). Likewise, the response of adenylate cyclase to isoproterenol in transplanted myocardium was not significantly different from that in normal myocardium, but the response was markedly depressed in cardiomyopathic myocardium. Although forskolin-stimulated adenylate cyclase activity was similar in all three groups, guanine nucleotide-stimulated adenylate cyclase activity was markedly reduced in transplanted myocardium (20 +/- 17 vs. 78 +/- 13 pmol/mg/min for normal myocardium, p less than 0.01) and to a lesser degree in cardiomyopathic myocardium (39 +/- 14 pmol/mg/min, p less than 0.03 vs. normal myocardium). Thus, there is no evidence of beta-adrenergic receptor up-regulation or supersensitivity in denervated transplanted human myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of the Purkinje-ventricular muscle junctional conduction by elevated potassium and hypoxia.
Authors: Tan R C , Ramza B M , Joyner R W
Published: June 2011

Action potential transmission in the canine ventricle normally occurs from the Purkinje (P) system into the ventricular muscle (VM) at specific P-VM junction sites. Transitional (T) cells are located between the Purkinje and the ventricular (V) cells at these P-VM junction sites. It has been shown that exposure to elevated [K+]0 in combination with hypoxia produces an increase in the P-VM conduction time. To examine this increase in P-VM conduction time, simultaneous measurements of the action potential upstrokes of T cells and the activation times of the local P and V cells at P-VM junctional sites were obtained from in vitro canine papillary muscles. The effects of elevated [K+]0 and hypoxia on conduction from P cells to T cells was then compared with the conduction from T cells to V cells to assess the relative contribution of each to the increase in the P-VM conduction time. We found that this intervention has approximately equal effects on the two sequential steps involved in P-VM conduction. We then analyzed the increased delay from T cells and V cells on the basis of three hypothetical mechanisms: 1) increased coupling resistance, 2) decreased V cell excitability, and 3) decreased cellular responsiveness of the T cells. Our results show that the effects of elevated [K+]0 and hypoxia on T-VM delay can be accounted for by a decreased responsiveness of the T cells without any significant electrical uncoupling between T and V cells or decrease in VM excitability.