bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective enhancement of the cardiac sympathetic response to exercise by anginal chest pain in humans.
Authors: McCance A J , Forfar J C
Published: June 2011

Cardiac and whole body [3H]norepinephrine kinetics were used to evaluate the response of overall and cardiac sympathetic activity to supine bicycle exercise in 31 patients with coronary artery disease (CAD) and in nine normal control subjects (group 1). Of the 31 patients with CAD, 20 developed evidence of myocardial ischemia during exercise (group 2), typical angina occurring in 20 of 20 and ischemic ST segment changes in 13 of 20, whereas 11 patients developed no evidence of ischemia (no chest pain or electrocardiographic changes) (group 3). Exercise resulted in increased total and cardiac NE spillover in all groups of patients. Basal cardiac NE spillover was similar in the three groups (group 1, 5 +/- 1 ng/min; group 2, 8 +/- 1 ng/min; group 3, 7 +/- 2 ng/min; p = NS), but during exercise, cardiac NE spillover was greater in patients who developed angina (group 2, 30 +/- 5 ng/min) than in those who did not (group 1, 17 +/- 2 ng/min; group 3, 17 +/- 2 ng/min; p less than 0.05). The increases in total NE spillover were similar in the three groups. Supine bicycle exercise increases cardiac and overall sympathetic tone in normal control subjects and in patients with CAD. The occurrence of angina selectively enhances the cardiac sympathetic response to exercise. In the absence of angina, patients with CAD and control subjects without CAD have similar sympathetic responses to exercise.
Detecting abnormalities in left ventricular function during exercise by respiratory measurement.
Authors: Koike A , Itoh H , Taniguchi K , Hiroe M
Published: June 2011

The degree of exercise-induced cardiac dysfunction and its relation to the anaerobic threshold were evaluated in 23 patients with chronic heart disease. A symptom-limited exercise test was performed with a cycle ergometer with work rate increased by 1 W every 6 seconds. Left ventricular function, as reflected by ejection fraction, was continuously monitored with a computerized cadmium telluride detector after the intravenous injection of technetium-labeled red blood cells. The anaerobic threshold (mean, 727 +/- 166 ml/min) was determined by the noninvasive measurement of respiratory gas exchange. As work rate rose, the left ventricular ejection fraction increased but reached a peak value at the anaerobic threshold and then fell below resting levels. Ejection fraction at rest, anaerobic threshold, and peak exercise were 41.4 +/- 11.3%, 46.5 +/- 12.0%, and 37.2 +/- 11.0%, respectively. Stroke volume also increased from rest (54.6 +/- 17.0 ml/beat) to the point of the anaerobic threshold (65.0 +/- 21.2 ml/beat) and then decreased at peak exercise (52.4 +/- 18.7 ml/beat). The slope of the plot of cardiac output versus work rate decreased above the anaerobic threshold. The anaerobic threshold occurred at the work rate above which left ventricular function decreased during exercise. Accurate determination of the anaerobic threshold provides an objective, noninvasive measure of the oxygen uptake above which exercise-induced deterioration in left ventricular function occurs in patients with chronic heart disease.
Effect of a critical coronary stenosis on myocardial neutrophil accumulation during ischemia and early reperfusion in dogs.
Authors: Richard V J , Brooks S E , Jennings R B , Reimer K A
Published: June 2011

In many experimental models of ischemia and reperfusion, reperfusion is performed abruptly, allowing full reactive hyperemia to occur. In the clinical setting, however, reperfusion after thrombolysis is often limited by residual stenosis. Some experimental models attempt to mimic this situation with a "critical stenosis" (defined as a coronary constriction sufficient to abolish reactive hyperemia without altering baseline flow). The purpose of this study was to determine whether preventing reactive hyperemia during the initial phase of reperfusion would modify the transmural distribution of myocardial blood flow or the myocardial accumulation of polymorphonuclear leukocytes (PMNs). The left circumflex artery was occluded for 90 minutes and then reperfused for 60 minutes in anesthetized, open-chest dogs. Autologous PMNs were isolated, labeled with 111In, and reinjected 1 hour before coronary occlusion. 125I-labeled albumin was injected simultaneously to correct for 111In associated with plasma proteins and to permit calculation of the number of PMNs in the inner, middle, and outer thirds of nonischemic and ischemic-reperfused tissue. The presence of a critical stenosis abolished reactive hyperemia during the first 5 minutes of reperfusion, but did not substantially affect blood flow measured after 55 minutes of reperfusion. In both groups, there was a significant accumulation of PMNs in all layers of the ischemic-reperfused bed compared with the nonischemic bed, and the magnitude of this PMN accumulation was not altered by the presence of a critical stenosis. Moreover, infarct size, estimated by triphenyl tetrazolium chloride (TTC) loss after 60 minutes of reperfusion, was not affected by the presence of a critical stenosis. Thus, the presence of a critical stenosis abolished the hyperemic blood flow after reperfusion but did not influence the early PMN response to ischemia and reperfusion or the early loss of TTC staining.
Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil-mediated reperfusion injury.
Authors: Litt M R , Jeremy R W , Weisman H F , Winkelstein J A , Becker L C
Published: June 2011

Reperfusion of ischemic myocardium may accelerate necrosis of injured myocytes. To determine the role of neutrophil leukocytes in this process, we examined whether neutrophil depletion during reperfusion could modify infarct size in anesthetized dogs. The proximal circumflex coronary artery was occluded for 90 minutes and then reperfused for 2 hours via an extracorporeal circuit with either whole blood (n = 11) or with blood depleted of neutrophils by leukocyte filters (n = 11). The leukocyte filters caused near-total neutropenia in blood reperfusing the ischemic myocardium (7 +/- 7 neutrophils/microliters compared with 2,551 +/- 317/microliters in controls, mean +/- SEM; p less than 0.001. Infarct size was measured by planimetry of myocardial slices stained with triphenyltetrazolium chloride (TTC), and the accuracy of TTC for identifying necrotic myocardium was verified by electron microscopy. The size of the ischemic risk region was the same in the control (41.6 +/- 1.0%) and neutropenic (41.8 +/- 2.1%) groups. Collateral blood flow to the risk region was the same in control (0.15 +/- 0.03 ml/min/g) and neutropenic (0.13 +/- 0.03 ml/min/g) groups. Among dogs with collateral flow less than 0.2 ml/min/g, infarct size was reduced in the neutropenic group (27.7 +/- 6.7% of risk region, n = 8), compared with control dogs (52.5 +/- 5.7%; n = 7; p = 0.02). Multiple linear regression described the relation between infarct size, risk region size, and collateral flow in the control group, and the same regression relation was used to predict infarct size for the neutropenic group. Mean predicted infarct size in the neutropenic group (n = 11) was 16.8 +/- 3.4% of left ventricle, whereas mean observed infarct size was 9.6 +/- 3.1% (p less than 0.01). The extent of the no-reflow zone (absence of thioflavin-S-fluorescence) was also less in the neutropenic than the control group (2.2 +/- 0.8% vs. 8.1 +/- 2.7% of the risk region, p less than 0.05). Neutropenia limited to the reperfusion period is associated with significant reductions in the extent of the infarct and no-reflow zones after 90 minutes of ischemia. These findings support the hypothesis that reperfusion necrosis occurs after prolonged myocardial ischemia and indicate that neutrophil leukocytes are important mediators of such reperfusion injury.
Sympathoadrenal inhibition by atrial natriuretic peptide is not attenuated during development of congestive heart failure in dogs.
Authors: Holtz J , Münzel T , Sommer O , Bassenge E
Published: June 2011

The feedback control of neuroendocrine activity by cardiopulmonary blood volume is disturbed in congestive heart failure. By analyzing plasma catecholamine kinetics, we tested in 11 chronically instrumented conscious dogs whether attenuations in the sympathoadrenal inhibition induced by atrial natriuretic peptide (ANP) contributed to this disturbance. Low-output failure was brought about by continuous ventricular pacing at 265 beats/min for 2 weeks. This resulted in a decline in aortic flow by 37 +/- 5% (SEM), an increase in peripheral vascular resistance by 48 +/- 4%, a 13 +/- 3-fold elevation in plasma ANP, a 9 +/- 3-fold elevation in plasma renin activity, and an augmentation of the norepinephrine-release rate into plasma by 132 +/- 17%. During ANP infusion, the epinephrine-release rate declined by 26 +/- 5% per 10-fold elevation in plasma ANP before pacing and by 31 +/- 7% (not significantly different) after 2 weeks of pacing. Before pacing, ANP attenuated plasma renin activity and caused hypotension without a rise in norepinephrine-release rate. After 2 weeks of pacing, ANP lowered norepinephrine release (by 16 +/- 6%) without affecting blood pressure or plasma renin activity, and vascular nonresponsiveness to ANP was verified under autonomic blockade. These data indicate that, during the development of heart failure, an inhibitory action of ANP on norepinephrine release is unmasked by an ANP-specific vascular desensitization, whereas the inhibition of epinephrine release is observed throughout. It is concluded that ANP-induced sympathoadrenal inhibition is not attenuated and, therefore, does not contribute to the disturbed regulation observed early in the development of failure.
Captopril restores hemodynamic responsiveness to atrial natriuretic peptide in rats with heart failure.
Authors: Raya T E , Lee R W , Westhoff T , Goldman S
Published: June 2011

Atrial natriuretic peptide levels are elevated in heart failure. However, the hemodynamic responses to exogenous atrial natriuretic peptide infusion in heart failure are blunted. To determine if captopril can restore hemodynamic responsiveness to atrial natriuretic peptide infusion in rats with heart failure, studies were performed in a rat model of heart failure after coronary artery ligation. Rats with heart failure received either captopril (2 g/l drinking water) or placebo for 4 weeks and then were treated with an infusion of atrial natriuretic peptide (0.3 microgram/kg/min). Captopril treatment alone improved hemodynamics. Left ventricular end-diastolic pressure, mean aortic pressure, and mean circulatory filling pressure decreased from 22 +/- 2 to 14 +/- 1, from 106 +/- 4 to 76 +/- 3, and from 10.5 +/- 0.6 to 8.8 +/- 0.4 mm Hg, respectively. Heart rate, right atrial pressure, and hematocrit were unchanged. Total blood volume decreased from 66.0 +/- 1.0 to 60.0 +/- 1.0 ml/kg; venous compliance increased from 2.1 +/- 0.1 to 2.7 +/- 0.1 ml/kg/mm Hg. Atrial natriuretic peptide alone had minimal hemodynamic effects on rats with heart failure. There was no change in right atrial pressure, mean aortic pressure, left ventricular end-diastolic pressure, mean circulatory filling pressure, and total blood volume. However, atrial natriuretic peptide infusion increased venous compliance from 2.1 +/- 0.1 to 2.4 +/- 0.1 ml/kg/mm Hg. Heart rate and hematocrit increased from 323 +/- 5 to 359 +/- 8 beats/min and from 48 +/- 1% to 51 +/- 1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Paradoxical effects of exercise on the QT interval in patients with polymorphic ventricular tachycardia receiving type Ia antiarrhythmic agents.
Authors: Kadish A H , Weisman H F , Veltri E P , Epstein A E , Slepian M J , Levine J H
Published: June 2011

We analyzed the results of exercise testing performed in the absence of all antiarrhythmic drugs in 11 case patients with newly documented polymorphic ventricular tachycardia in response to type Ia antiarrhythmic agents. These results were compared with those found in 11 control patients matched for age, sex, and heart disease to determine whether the response of the QT interval to exercise testing was abnormal in patients who developed worsening of arrhythmia while taking antiarrhythmic drugs. QT, RR, and QTc intervals (by Bazett's method) were evaluated at rest and at 3 minutes of exercise in both groups. At rest, there was no significant difference in the QT interval (410 +/- 13 vs. 386 +/- 11 msec), RR interval (890 +/- 56 vs. 781 +/- 43 msec), or corrected QT interval (438 +/- 10 vs. 438 +/- 4 msec) in the case patients and the control patients. Both groups demonstrated a similar chronotropic response to exercise. The QT interval shortened in both groups with exercise (p less than 0.001), but the degree of shortening tended to be greater in the control patients (to 310 +/- 9 msec) than in the case patients (to 357 +/- 11 msec) (p = 0.06). Thus, there was a paradoxical increase in the QTc interval in the patients who experienced a proarrhythmic effect of type Ia drugs but not in the control patients (to 482 +/- 8 vs. 431 +/- 5 msec; p less than 0.001). Ten of 11 case patients but only one of 11 control patients had an increase in QTc interval of more than 10 msec with exercise (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Occurrence of oxidative stress during reperfusion of the human heart.
Authors: Ferrari R , Alfieri O , Curello S , Ceconi C , Cargnoni A , Marzollo P , Pardini A , Caradonna E , Visioli O
Published: June 2011

We have investigated the relation between occurrence of myocardial oxidative stress and functional recovery during postischemic reperfusion in 20 selected patients subjected to aortocoronary bypass grafting. Patients were selected for having normal percent ejection fraction and left ventricular end-diastolic pressure before the operation. Occurrence of oxidative stress was assessed by measuring the formation and release of oxidized glutathione (GSSG) in the coronary sinus immediately before aortic cross-clamp, 1, 5, 10, and 20 minutes after removal of aortic cross-clamp, and 10 and 20 minutes after the end of cardiopulmonary bypass. Reduced glutathione (GSH), lactate, and creatine phosphokinase release were also monitored with the same timing. Standard hemodynamic measurements were recorded by means of a triple-lumen thermodilution pulmonary artery catheter before sternotomy, 15 minutes after the end of cardiopulmonary bypass, and during the 24 hours after termination of cardiopulmonary bypass. Reperfusion in patients after a short period of ischemia (less than 30 minutes; group 1) resulted in a small and transient release in the coronary sinus of GSSG and GSH and in a progressive improvement of hemodynamic parameters reaching a stable state 4 hours after the operation. In patients with a period of ischemia longer than 30 minutes (group 2), reperfusion induced a marked and sustained release of lactate, GSH, and GSSG; the arteriocoronary sinus difference for GSSG was still negative after the end of cardiopulmonary bypass. The arteriocoronary sinus difference for creatine phosphokinase also remained negative for as long as 20 minutes after cardiopulmonary bypass, and the rate of functional recovery was significantly delayed, reaching the values of group 1 only 12 hours after the operation. In these patients there was a positive correlation (r = 0.88, p less than 0.01) between the duration of ischemia and the myocardial arteriovenous difference for GSSG. In addition, there was a negative correlation between the arteriocoronary sinus difference for GSSG and cardiac index measured 2, 4, and 6 hours after the operation. These data suggest for the first time that, depending on the severity of the ischemic period, oxidative stress occurs during reperfusion of patients with coronary artery disease who are subjected to heart surgery and that it may be linked with a delay in postoperative recovery of cardiac function.
Assessment of left ventricular relaxation by Doppler echocardiography. Comparison of isovolumic relaxation time and transmitral flow velocities with time constant of isovolumic relaxation.
Authors: Myreng Y , Smiseth O A
Published: June 2011

Isovolumic relaxation time (IVRT) and events of early transmitral flow measured by Doppler echocardiography were validated against the time constant of left ventricular relaxation (tau) in open-chest dogs. During increased inotropy (by isoproterenol infusion) at constant preload, enhancement of relaxation was indicated by a decrease in tau from 48 +/- 12 (mean +/- SD) to 33 +/- 5 msec (p = 0.04) with a concomitant decrease in IVRT from 74 +/- 18 to 38 +/- 8 msec (p = 0.03). During decreased inotropy (by propranolol infusion) at constant preload, slowing of relaxation was indicated by an increase in tau from 40 +/- 8 to 51 +/- 13 msec (p = 0.02) with a concomitant increase in IVRT from 71 +/- 15 to 83 +/- 21 msec (p less than 0.05). A significant correlation between changes in tau and changes in IVRT was found (r = 0.66, p less than 0.001). In contrast, when left ventricular end-diastolic pressure was increased from 7 +/- 2 to 24 +/- 4 mm Hg at constant inotropy, tau increased from 47 +/- 14 to 64 +/- 25 msec (p = 0.03), whereas no change in IVRT was observed (76 +/- 19 and 71 +/- 19 msec, respectively). Aortic pressure was not significantly changed during any intervention, and heart rate was kept constant by pacing. Peak early transmitral velocity was unchanged by propranolol but increased during isoproterenol and saline infusion (p less than 0.001 and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of a vasopressin antagonist with combined antipressor and antiantidiuretic activities in rats with left ventricular dysfunction.
Authors: Mulinari R A , Gavras I , Wang Y X , Franco R , Gavras H
Published: June 2011

These experiments assessed the hemodynamic and aquaretic effects of an arginine vasopressin (AVP) antagonist with dual V1V2-receptor inhibiting properties in rats with congestive heart failure resulting from ischemic cardiomyopathy. The compound d(CH2)5-D-Tyr(Et)VAVP was used in these studies. Rats with limited or extensive myocardial infarcts (i.e., with less than 50% or greater than 66% necrosis of the left ventricular wall, respectively, induced by left coronary ligation) and sham-operated controls received the AVP antagonist (100 micrograms/kg i.v.) 4 weeks later. This agent produced an 18% increase in cardiac output (p less than 0.05) and 13% decrease in systemic vascular resistance in the severely damaged rats, both changes being significantly different from those seen in the normal controls or the rats with limited infarcts. All animals exhibited increases in urinary output of 4-10-fold over baseline. We conclude that the hemodynamic and renal effects of this agent are beneficial in animals with left ventricular dysfunction.
Autoregulation of cardiac output by passive elastic characteristics of the vascular capacitance system.
Authors: Rothe C F , Gaddis M L
Published: June 2011

After a change in cardiac output, the magnitude of potential blood volume redistribution was investigated in 10 dogs anesthetized with chloralose. All of the venous return was pumped into a reservoir, using servocontrolled pumps to maintain fixed superior and inferior vena cava pressures. The cardiac output was set at various levels by pumping from the reservoir into the right atrium. Changes in reservoir volume were assumed to reflect the changes in vascular blood volume. After measuring the control responses, cardiovascular reflexes were blocked with hexamethonium. Reducing the cardiac output, for example, from 110 to 80 ml/(min.kg) with reflexes intact, caused a 9.2-ml/kg transfer of blood from the dog to the reservoir. With reflexes blocked, the same change in cardiac output caused 6.8 ml/kg of the blood to be transferred. Under the control conditions, throughout the range of 50-140 ml/(min.kg), an increase or decrease of cardiac output of 1 ml/(min.kg) elicited a 0.304 +/- 0.086 (mean +/- SD) ml/kg change in dog blood volume; with reflexes blocked, the flow sensitivity was 0.239 +/- 0.062 ml/kg. Thus, only 21% of the total blood volume redistribution was attributable to active reflex responses. Deterioration of the preparation may have attenuated the magnitude of active reflex activity. Neither the systemic vascular compliance of 1.80 +/- 0.35 ml/mm Hg.kg nor the fraction of venous return from the superior vena cava of 26.5 +/- 4.6% was significantly changed by reflex blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics in humans.
Authors: Matsuyama K , Yasue H , Okumura K , Matsuyama K , Ogawa H , Morikami Y , Inotsume N , Nakano M
Published: June 2011

Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics were examined in 11 patients with angiographically normal coronary arteries and without variant angina or resting angina. Selective H1-receptor stimulation was achieved by infusing histamine into the left coronary artery at a rate of 2.0 micrograms/min for 5 minutes after pretreatment with cimetidine (25 mg/kg). Plasma histamine concentration in the coronary sinus, coronary sinus blood flow, heart rate, and aortic pressure were measured before, during, and after the histamine infusion. Coronary arterial diameter was measured by cinevideodensitometric analysis of coronary arteriograms performed before and immediately after the histamine infusion. During the histamine infusion, plasma histamine concentration in the coronary sinus increased from 0.33 +/- 0.06 to 5.86 +/- 0.71 ng/ml (p less than 0.01); coronary sinus blood flow increased from 98 +/- 12 to 124 +/- 13 ml/min (p less than 0.01), and coronary vascular resistance decreased from 1,113 +/- 117 to 851 +/- 91 mm Hg.min/l (p less than 0.01). Heart rate and aortic pressure remained unchanged. The mean luminal diameters of the proximal, middle, and distal left anterior descending artery increased by 9.4 +/- 3.6% (p less than 0.05), 19.2 +/- 3.8% (p less than 0.001), and 31.5 +/- 5.6% (p less than 0.001), respectively, after the histamine infusion. The mean luminal diameters of the proximal, middle, and distal left circumflex artery increased by 15.2 +/- 3.6% (p less than 0.01), 17.5 +/- 5.2% (p less than 0.01), and 20.6 +/- 4.3% (p less than 0.001), respectively, after the histamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
An analysis of the cost effectiveness of the implantable defibrillator.
Authors: Kuppermann M , Luce B R , McGovern B , Podrid P J , Bigger J T , Ruskin J N
Published: June 2011

The automatic implantable defibrillator has been shown to decrease the mortality of patients who have survived cardiac arrest due to ventricular tachycardia or fibrillation and are at high risk for recurrence. We performed a cost-effectiveness analysis of this seemingly expensive new technology with data obtained from the 1984 Medicare data base, the medical literature, Medicare carriers, individual pharmacies and hospitals, and expert opinion. Analyzing combinations of principal and secondary discharge diagnoses across 18 diagnosis-related groups, we estimated the cost of hospitalization for a comparison group of patients. Hospitalization costs for the defibrillator group were obtained from reported empirical data. Rehospitalization rates and other health-care use estimates were solicited from an expert panel of physicians, and mortality rates for both groups were obtained from the literature. Using a decision-analytic model, we estimated that the net cost effectiveness of the defibrillator, when used in the high-risk patient, is approximately $17,100 per life-year saved, with sensitivity analyses suggesting that the true value lies between $15,000 and $25,000. This estimate is well within the range that is currently accepted by the US medical care system for other life-saving interventions. We also estimated the cost effectiveness of the defibrillator in a 1991 scenario to be $7,400 per life-year saved, when the device would have greater longevity, would be programmable, and would not require a thoracotomy. Sensitivity analyses suggest that the true value lies between a value that is cost saving (less expensive than pharmacologic therapy) and $19,600 per life-year saved.
Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts. Lipid and nonlipid factors.
Authors: Blankenhorn D H , Alaupovic P , Wickham E , Chin H P , Azen S P
Published: June 2011

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease--total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure--had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug- and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-III in high density lipoproteins of drug-treated subjects. Both drug- and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis.
Doppler studies of vena cava flows in human fetuses. Insights into normal and abnormal cardiac physiology.
Authors: Reed K L , Appleton C P , Anderson C F , Shenker L , Sahn D J
Published: June 2011

We examined vena cava Doppler flow velocity tracings from 69 fetuses between 22 and 40 weeks' gestation. Twenty-three fetuses had arrhythmias. Fifteen fetuses had absent end-diastolic Doppler velocities in the umbilical artery, a condition associated with intrauterine growth retardation, and 15 normal fetuses with normal umbilical artery Doppler velocity ratios were matched by gestational age. In studies in 16 additional fetuses, inferior vena cava Doppler velocity waveforms were compared with superior vena cava Doppler velocity waveforms. Peak velocities and time-velocity integrals of forward or reverse flow during systole, early diastole, and atrial contraction were measured. In addition, the time-velocity integral during flow coincident with atrial contraction (a wave) was expressed as a percent of the time-velocity integral of total forward flow during both systole and early diastole. Systolic-to-diastolic ratios of inferior vena cava forward time-velocity integrals were not significantly different from systolic-to-diastolic ratios of superior vena cava forward time-velocity integrals (p = 0.86), but the percent of blood moving in a reverse direction during atrial contraction in the inferior vena cava was greater than the percent of blood moving in a reverse direction in the superior vena cava (p less than 0.05). Relative forward flow in early diastole in the group of normal fetuses increased with advancing gestational age (r = 0.60, p less than 0.05). During premature atrial contractions flow in the inferior vena cava was reversed, and the percent of reverse flow during atrial systole increased significantly from 4.5 +/- 0.3% to 28.3 +/- 3.7% (mean +/- SEM, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Mildly dilated congestive cardiomyopathy. Use of prospective diagnostic criteria and description of the clinical course without heart transplantation.
Authors: Keren A , Gottlieb S , Tzivoni D , Stern S , Yarom R , Billingham M E , Popp R L
Published: June 2011

Prognosis in classically described dilated congestive cardiomyopathy has been reported to be related to ventricular size. Mildly dilated congestive cardiomyopathy (MDCM) has been defined as end-stage heart failure of unknown etiology (New York Heart Association class IV, left ventricular ejection fraction less than 30%), occurring with neither typical hemodynamic signs of restrictive myopathy nor significant ventricular dilatation (less than 15% above normal range). The present study includes follow-up in 12 nontransplant patients. In the first 4 months after diagnosis, two patients improved and are living, and two showed cardiac dilation and clinical deterioration and died. Six of the remaining eight with persistent MDCM died (four with intractable heart failure and two, sudden deaths) without change in ventricular size before death, despite medical therapy over 20 +/- 8 months. Eight comparable transplanted patients with persistent MDCM demonstrated improved total survival by life table analysis (p less than 0.05). A family history of congestive cardiomyopathy was found in nine of 16 patients (56%) with persistent MDCM. Nontransplant patients were older (p less than 0.02), but other findings were similar in the two groups. Endomyocardial biopsies available in 14 of 16 cases showed little or no myofibrillar loss in spite of severe hemodynamic impairment. The degree of myofibrillar loss did not correlate with hemodynamic parameters but showed good correlation with left ventricular size, that is, five of six patients with no myofibrillar loss had normal ventricular size, whereas all eight patients with mild myofibrillar loss had mild cardiomegaly (p less than 0.002). Our current experience suggests a somewhat variable but negative prognosis after prospective diagnosis of MDCM, with poor survival in patients with persistence of the original diagnostic features during follow-up. Preservation of heart size in MDCM is probably related to lack of significant myofibrillar loss. Thus, irrespective of heart size or myofibrillar preservation on biopsy, heart transplantation should be strongly considered in MDCM if signs of severe cardiac dysfunction persist despite therapy.
Lack of diurnal variation in the onset of non-Q wave infarction.
Authors: Kleiman N S , Schechtman K B , Young P M , Goodman D A , Boden W E , Pratt C M , Roberts R
Published: June 2011

Data concerning the time of onset of myocardial infarction were obtained for 540 of the 544 patients with creatinine kinase (CK)-MB-confirmed non-Q wave myocardial infarction enrolled in the multicenter Diltiazem Reinfarction Study. Data were also collected for 627 patients who were screened but excluded. Among the 1,167 patients, no diurnal pattern of onset could be found at either 2- or 6-hour intervals. Among the 540 patients enrolled in the trial, no pattern could be found at these intervals either, although at 8-hour intervals, 27% of infarctions occurred between midnight and 8:00 AM, compared with 37% between 8:00 AM and 4:00 PM and 36% between 4:00 PM and 12:00 AM (p = 0.02). In contrast to the patterns previously noted for Q wave myocardial infarction, there was no preponderance of non-Q wave infarction in the late morning. Circadian rhythm was also absent among patients not treated with beta-blockers as well as among patients presenting with ST segment elevation on their enrollment electrocardiograms. Diabetics, women, and patients with first infarction were more likely to present during the afternoon hours. We conclude that the late morning preponderance seen for Q-wave myocardial infarction is not discernable in patients with non-Q wave myocardial infarction. This observation suggests that the pathogenesis of these two infarct subtypes is different or that the process of thrombotic coronary occlusion in Q wave infarction (sustained) differs from that in non-Q wave infarction (nonsustained).
Antiplatelet antibody [7E3 F(ab')2] prevents rethrombosis after recombinant tissue-type plasminogen activator-induced coronary artery thrombolysis in a canine model.
Authors: Mickelson J K , Simpson P J , Cronin M , Homeister J W , Laywell E , Kitzen J , Lucchesi B R
Published: June 2011

Coronary artery rethrombosis can complicate initially effective thrombolytic therapy. Platelets interacting with injured vascular endothelium in a region along the coronary artery with reduced luminal cross-sectional area contribute to rethrombosis. The purpose of this study was to investigate the potential of the F(ab')2 fragment of the murine monoclonal antibody 7E3 [7E3 F(ab')2] to prevent rethrombosis after intracoronary clot lysis with recombinant tissue-type plasminogen activator (rt-PA) in an experimental model. The 7E3 F(ab')2 binds to the platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa), thereby preventing platelet-fibrinogen interaction and intravascular thrombus formation. Experimental coronary artery thrombosis was produced in the anesthetized dog by application of direct anodal current to the intimal surface of the left circumflex coronary artery in the region of an external stenosis. Lysis of the established intracoronary thrombus was achieved with the intravenous administration of rt-PA (25 mg) after which the animals were randomized into two groups. Group 1 (n = 10) served as the control, receiving the saline diluent, and group 2 (n = 9) received 7E3 F(ab')2, given as a single intravenous injection (0.8 mg/kg). The times required for occlusive thrombus formation, rt-PA-induced thrombolysis, and rethrombosis (if it occurred) were similar in the animals treated with saline and those treated with 7E3 F(ab')2. The initial left circumflex coronary artery blood flow was similar in both groups but decreased to a negligible level in group 1. In group 2, left circumflex coronary artery blood flow declined modestly (24 +/- 2 to 10 +/- 2 ml/min). Rethrombosis occurred in all animals in group 1 but in only two of nine animals in group 2 (p less than 0.05). Oscillations in coronary blood flow preceded rethrombosis in group 1, whereas 7E3 F(ab')2 stabilized left circumflex coronary artery blood flow patterns during the course of teh experimental protocol (5.2 +/- 0.9 vs. 0.7 +/- 0.4 oscillations, respectively; p less than 0.05). Thrombus mass recovered from the left circumflex coronary artery at the conclusion of each experiment was greater in group 1 as compared with group 2 (7.0 +/- 2.3 vs. 1.5 +/- 0.7 mg, respectively; p less than 0.05). The area of left ventricle at risk for infarction was similar in both groups but infarct size, infarction/at risk assessed histochemically, was larger in group 1 than group 2 (35 +/- 9% vs. 6 +/- 4%, respectively; p less than 0.05). Platelet aggregation induced by ADP and arachidonic acid was similar at baseline for all of the animals.(ABSTRACT TRUNCATED AT 400 WORDS)
Myocardial kinetics of Tc-MIBI in canine myocardium after dipyridamole.
Authors: Glover D K , Okada R D
Published: June 2011

Technetium 99m-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-MIBI) is a promising new myocardial perfusion imaging agent producing excellent rest images. Imaging, however, will need to be performed with exercise or dipyridamole to detect ischemia and to differentiate salvaged but still ischemic myocardium from scar. Accordingly, 12 dogs were given mild-to-moderate left circumflex coronary stenoses (group 2), and 10 dogs were given severe stenoses (group 3). In five control dogs (group 1), there was no stenosis. After an intravenous infusion of dipyridamole (0.08 mg/kg/min for 4 minutes), Tc-MIBI was injected into the right atrium. Over the next 4-hour study period, myocardial Tc-MIBI activities were continuously monitored in both the left anterior descending (LAD) (normal) and left circumflex (LCx) (ischemic) coronary artery (ischemic) zones using miniature cadmium telluride radiation detectors and serial gamma camera images were acquired when necessary. Tc-MIBI was rapidly taken up by nonischemic, mild-to-moderate, and severe ischemic myocardium. The initial myocardial uptake of Tc-MIBI was linearly related (r = 0.97) to regional myocardial blood flow at rates up to 2.0 ml/min/g. After the initial uptake, the mean 4-hour fractional myocardial clearance was similar between the control (0.09 +/- 0.03 [+/- SEM]) and group 2 (0.07 +/- 0.03) and group 3 (0.09 +/- 0.03) ischemic zones. Tc-MIBI blood clearance was rapid and biexponential with an initial fast clearance phase followed by a slow clearance phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Microcinephotography of the developing heart in neural crest-ablated chick embryos.
Authors: Leatherbury L , Gauldin H E , Waldo K , Kirby M L
Published: June 2011

Microcinephotography was used to study heart development in a neural crest model of heart defects, that is, persistent truncus arteriosus, interrupted aortic arch, double outlet right ventricle, or single ventricle and tricuspid valve anomalies. These defects were created in chick embryos by ablation of premigratory neural crest destined for the aorticopulmonary and truncal septa, as well as the third and fourth aortic arch arteries. When embryogenesis reached the looped cardiac tube stage of development (Hamburger-Hamilton stage 18), 19 experimental and 15 control embryos were filmed at 100 frames per second under controlled environmental conditions. Analysis of the microcinephotography films showed the following significant distinguishing characteristics of the developing heart in the experimental embryos: altered conotruncal shape in 100%, depressed contractility and dilation of the primitive ventricle in 84%, decreased emptying of the bulbus cordis in 79%, incompetent truncal cushions in 68%, incomplete looping of the cardiac tube in 58%, and fourth right aortic arch artery without blood flow and third right aortic arch artery with increased flow in 53%. These abnormal characteristics suggested that there were functional and morphological changes in the developing heart of experimental embryos before the time when the predicted structural heart defects would be apparent. It is proposed that the primitive ventricle might attempt to compensate for depressed contractility by ventricular dilation. The incompetent truncal cushions could be secondary to the depressed contractility or secondary to the neural crest ablation that is known to cause persistent truncus arteriosus, an interrupted aortic arch, or both. The absence of blood flow in the right fourth aortic arch artery that will become the definitive aorta correlates with the expected incidence of interrupted aortic arches in this neural crest-ablation model of heart defects. It is speculated that the incomplete looping of the cardiac tube might hinder normal developmental alignment of the outflow and inflow tracts, producing a spectrum of lesions of maldevelopment of the tricuspid valve and dextroposition of the aorta.
Trapidil in preventing restenosis after balloon angioplasty in the atherosclerotic rabbit.
Authors: Liu M W , Roubin G S , Robinson K A , Black A J , Hearn J A , Siegel R J , King S B
Published: June 2011

Trapidil (triazolopyrimidine) possesses activity against platelet-derived growth factor-induced cellular proliferation in vitro and intimal proliferation in vivo. The objective of this study was to determine if trapidil could prevent restenosis in experimentally induced atherosclerotic rabbits. New Zealand White rabbits with preexisting iliac arterial lesions induced by balloon deendothelialization underwent balloon angioplasty. Arteriography was performed before, immediately after, and 4 weeks after the balloon dilatation. Tissue sections of the dilated arterial segment were also analyzed morphometrically. Seventeen rabbits were randomized to two groups: a control group (n = 8) and a trapidil-treated group (n = 9). The treatment group received 30 mg/kg s.c. trapidil twice daily. The angiographic luminal diameters before and after dilatation were similar. At the 4-week restudy, there was a significant preservation of luminal diameter in the trapidil group compared with the control group (1.27 +/- 0.20 vs. 0.94 +/- 0.48 mm, respectively; p less than 0.005). When luminal diameters immediately after dilatation were compared with diameters at the 4-week restudy (i.e., when the degree of restenosis was assessed), there was a greater luminal diameter reduction in the control group than in the trapidil group (0.70 +/- 0.44 vs. 0.30 +/- 0.25 mm, respectively; p = 0.005). By morphometric analyses, the luminal areas were also greater in the trapidil group than the control group (0.80 +/- 0.25 vs. 0.57 +/- 0.33 mm2, respectively; p = 0.03). Intimal thickness was significantly less for the trapidil group than for the control group (0.33 +/- 0.15 vs. 0.44 +/- 0.15 mm, respectively; p = 0.01), as well as medial thickness (0.09 +/- 0.03 vs. 0.11 +/- 0.03 mm, respectively; p = 0.01). In this study, trapidil significantly increased the luminal area and reduced the intimal thickness in the atherosclerotic rabbit iliac artery after balloon angioplasty.
Frequency-dependent effects of quinidine on the ventricular action potential and QRS duration in humans.
Authors: Nademanee K , Stevenson W G , Weiss J N , Frame V B , Antimisiaris M G , Suithichaiyakul T , Pruitt C M
Published: June 2011

We studied the frequency-dependent effects of quinidine on the right ventricular action potential and QRS duration in 10 patients (nine men and one woman; mean age, 57 +/- 14 years) undergoing electrophysiologic studies for clinical indications. The right ventricular monophasic action potential, electrocardiographic, and conventional intracardiac electrical signals from various sites were recorded at different pacing cycle lengths from 30 seconds to 1 minute before and after a 10-mg/kg i.v. quinidine infusion. We used the extrastimulus technique to determine the effects of quinidine on ventricular refractory periods at different pacing cycle lengths and on the abrupt changes of the action potential duration. The action potential duration progressively decreased as the ventricular pacing rate increased at baseline and after quinidine infusion. Quinidine significantly increased the action potential duration from that of control by 25 msec (p less than 0.02) at the relatively slow pacing cycle lengths of 600, 500, and 400 msec. Quinidine's effect on the action potential duration was attenuated at the pacing cycle length of 350 msec and became negligible at 300 msec. In contrast, quinidine progressively lengthened the QRS duration as the pacing rate increased (20, 18, 37, 46, and 34 msec at pacing cycle lengths of 600, 500, 400, 350, and 300 msec, respectively; p less than 0.05). There were no rate-dependent changes in the QRS duration during the control period. The relation between the ventricular refractory periods and the action potential duration at different pacing cycle lengths was also determined before and after quinidine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Value of acceleration flows and regurgitant jet direction by color Doppler flow mapping in the evaluation of mitral valve prolapse.
Authors: Yoshida K , Yoshikawa J , Yamaura Y , Hozumi T , Shakudo M , Akasaka T , Kato H
Published: June 2011

To clarify the role of color Doppler echocardiography in the evaluation of mitral valve prolapse, we studied 49 consecutive patients in whom the sites of mitral valve prolapse were confirmed at the time of operation. The study group consisted of 22 patients with anterior leaflet prolapse, 24 patients with posterior leaflet prolapse, and three patients with multiple scallop prolapse (one patient with both anterior leaflet and middle scallop prolapse, and two patients with both medial and lateral scallop prolapse). Two-dimensional echocardiographic diagnosis of anterior leaflet prolapse was correct in all patients. The diagnosis of posterior leaflet prolapse by two-dimensional echocardiography, however, was mistaken as anterior leaflet prolapse in 16 (13 patients with medial scallop prolapse and three patients with lateral scallop prolapse) of the 24 patients according to current diagnostic criteria for mitral valve prolapse. Eight patients with middle scallop prolapse were diagnosed correctly by two-dimensional echocardiography. Acceleration flows in the left ventricle were observed by color Doppler echocardiography in all 49 patients. The sites of acceleration flows detected by color Doppler echocardiography coincided with those of prolapse confirmed in all at the time of operation. There was a significant correlation between the maximum area of acceleration flow signals and severity of mitral regurgitation estimated by angiography. In the 13 patients with medial scallop prolapse and the three patients with lateral scallop prolapse, a regurgitant jet originated from a bulged portion of the posterior leaflet and was directed toward the opposite left atrial cavity to the bulged portion by short-axis images of color Doppler echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)
Resting electrocardiographic abnormalities suggestive of asymptomatic ischemic heart disease associated with non-insulin-dependent diabetes mellitus in a defined population.
Authors: Scheidt-Nave C , Barrett-Connor E , Wingard D L
Published: June 2011

The prevalence of ischemic heart disease (IHD) in older adults by glucose tolerance status was evaluated in 2,223 white men and women, aged 50-89 years, in the Rancho Bernardo cohort who were studied between 1984 and 1987. Impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) were classified according to World Health Organization criteria. End points of ischemic heart disease were defined by Rose Questionnaire and resting electrocardiogram (ECG) according to the Minnesota Code. IHD by electrocardiographic changes was classified as asymptomatic (without history of chest pain or overt IHD) or symptomatic (with history). IHD by all criteria combined was significantly more common in men and women with NIDDM, and in women with IGT, than in those with normal glucose tolerance. The prevalence of myocardial infarction, defined by major Q wave, Rose Questionnaire chest pain criteria, or personal history, was higher in persons with NIDDM than in persons without; the difference was highly significant in women (odds ratio, 2.08 [1.22, 3.56]; p = 0.009). Angina pectoris was not significantly related to NIDDM or IGT in either sex. Electrocardiographic evidence of asymptomatic IHD was significantly more prevalent in both men and women with NIDDM as compared with those with normal glucose tolerance (odds ratios, 1.75 [1.10, 2.81] for men and 1.80 [1.07, 3.01] for women; p less than 0.05). This significant association persisted after excluding persons on digitlis or diuretic therapy and, in women, was also independent of the effect of major known IHD risk factors. These population-based data are consistent with clinical reports suggesting an association of diabetes with silent myocardial infarction or ischemia. The presence of ischemic resting electrocardiographic abnormalities in the asymptomatic diabetic patient is likely to have prognostic and therapeutic implications.