bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased plasma concentrations of platelet factor 4 in coronary artery disease: a measure of in vivo platelet activation and secretion.
Authors: Levine S P , Lindenfeld J , Ellis J B , Raymond N M , Krentz L S
Published: June 2011

Previous studies have shown that there is both a significant shortening in platelet survival and a measured hyperactivity to platelet-aggregating agents in patients with documented coronary artery disease compared with control groups. We used a recently described radioimmunoassay for the platelet-secreted protein platelet factor 4 (PF4) to study 162 patients with documented coronary artery disease. There was a significant increase in plasma PF4 concentrations in patients with documented coronary artery disease compared with angiographically normal patients (8.7 vs 16 ng/ml, respectively, n = 121), but as in previous studies of platelet survival, we could not correlate elevated plasma PF4 concentration and the severity or site of the coronary artery disease. In addition, there was no correlation with left ventricular function, serum cholesterol or the type of angina. Patients with confirmed acute myocardial infarction had no significant difference in mean plasma PF4 concentrations compared with similar groups of coronary disease patients who had prolonged chest pain or chronic stable angina. Coronary artery bypass grafting in a subgroup of patients did not affect the mean plasma PF4 concentration during 1 year of follow-up after bypass surgery, but medical therapy for angina with increasing doses of propranolol and nitrates significantly reduced PF4 concentration in another subgroup of patients who were not considered to be candidates for surgical therapy.
Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy.
Authors: Bonow R O , Rosing D R , Bacharach S L , Green M V , Kent K M , Lipson L C , Maron B J , Leon M B , Epstein S E
Published: June 2011

Verapamil improves exercise capacity in patients with hypertrophic cardiomyopathy (HCM), but its mechanism of action are unknown. We examined the effects of oral verapamil (320-480 mg/day) on resting left ventricular (LV) systolic and diastolic function in patients with HCM. High-temporal-resolution time-activity curves from gated technetium-99m radionuclide angiograms were analyzed before and after verapamil therapy in 40 patients, of whom 16 were also studied during propranolol therapy (80-960 mg/day). All but one patient had normal or supranormal systolic function, but 70% had evidence of diastolic dysfunction, defined as peak LV filling rate (PFR) less than 2.5 end-diastolic volumes (EDV)/sec or time to PFR greater than 80 msec. Verapamil did not change LV ejection fraction, peak ejection rate or ejection time, but did increase PFR (control 3.3 +/- 1.0 EDV/sec, verapamil 4.1 +/- 1.1 EDV/sec; p less than 0.001) and reduce time to PFR (control 187 +/- 56 msec, verapamil, 159 +/- 34 msec; p less than 0.001). Only 30% of patients had evidence of diastolic dysfunction during verapamil. In contrast, propranolol did not change LV ejection fraction, PFR or time to PFR, but did prolong ejection time and reduce peak ejection rate. Thus, LV diastolic filling is abnormal in a high percentage of patients with HCM, and verapamil normalizes or improves these abnormalities without altering systolic function. This mechanism may contribute to the clinical improvement of many HCM patients during verapamil therapy.
His-ventricular dissociation in a patient with reciprocating tachycardia and a nodoventricular bypass tract.
Authors: Morady F , Scheinman M M , Gonzalez R , Hess D
Published: June 2011

A patient with recurrent bouts of atrial fibrillation and wide-complex regular tachycardia underwent electrophysiologic studies. Premature atrial stimulation or atrial pacing during sinus rhythm resulted in gradual lengthening of the PR and AH intervals, narrowing of the HV interval and progressive preexcitation with a left bundle branch block and left-axis contour. Induction of tachycardia was dependent on critical delay in the atrioventricular interval and was associated with attainment of a maximal preexcitation pattern. During tachycardia, the ventriculoatrial interval was constant, whereas the interval from His bundle deflection to the ventricular complex was variable. We postulate that the tachycardia circuit involved reciprocation within the atrioventricular node and that a nodoventricular bypass tract was present in close anatomic or functional association with the slow atrioventricular nodal pathway. Our data suggest that both the nodoventricular bypass tract and the His-Purkinje system may be passive "bystanders" rather than essential components of the tachycardia circuit. In addition, although HV dissociation usually implies ventricular tachycardia, this case demonstrates that HV dissociation during wide-complex regular tachyarrhythmia is not diagnostic of ventricular tachycardia.
Primary oxalosis with pan-conduction cardiac disease: electrophysiologic and anatomic correlation.
Authors: Massie B M , Bharati S , Scheinman M M , Lev M , Desai J , Rubeson E , Schmidt W
Published: June 2011

A 27-year-old man with primary oxalosis and extensive visceral involvement was maintained on long-term chronic hemodialysis. He had an episode of presyncope associated with electrocardiographic findings of an erratic atrial rhythm, atrioventricular dissociation due to an accelerated junctional rhythm and right bundle branch block. Electrophysiologic studies showed irregular atrial depolarizations probably associated with multiple atrial pacemakers, atrial inexcitability, atrioventricular dissociation and infranodal conduction delay. These findings correlated well with extensive oxalate infiltration of the sinoatrial node and its approaches, the atrial preferential pathways, the approaches to the atrioventricular node, the atrioventricular node, and the His bundle and bundle branches. This is the first reported case of cardiac electrophysiologic abnormalities due to oxalate infiltration in a patient with primary oxalosis.
Transvenous angioplasty of experimental branch pulmonary artery stenosis in newborn lambs.
Authors: Lock J E , Niemi T , Einzig S , Amplatz K , Burke B , Bass J L
Published: June 2011

A dilatable form of bilateral branch pulmonary artery stenosis was created in 27 newborn lambs. Nine lambs were long-term survivors and were dilated with modified Grüntzig balloon dilation catheters. They were allowed to recover for 6-9 weeks, during which time there was no significant change in the mean systolic gradients across the narrowed sites. Thirteen arteries underwent dilation. Dilation was associated with a decrease in the systolic gradient in all cases (from 34.9 mm Hg to 8.1 mm Hg) and an increase in the diameter of the narrowed site (from 4.6 to 7.6 mm) as estimated by angiography. Flows and flow distribution were measured in four lambs before and after unilateral dilation using 15-mu radiolabeled microspheres; in each case, the fraction of total flow to the dilated lung rose after dilation (19.2 to 45.4%), as did the total flow to the dilated lung (30.0 to 69.2 ml/kg-min). Four lambs were catheterized every 2-4 weeks for an average of 16 weeks after dilation; the average gradient in these lambs remained below 10 mm Hg despite considerable growth (from 9.6 to 25.9 kg). Gross pathologic examination showed an intact vascular adventitia in all cases; there were multiple linear tears in the intima in recently (less than 7 days) dilated cases, but complete intimal healing had occurred by 2 months after dilation. No significant morbidity could be attributed to the dilation procedure. These results indicate that clinical trials are warranted.
Ventricular diastolic pressure-volume relations and the pericardium. Effects of changes in blood volume and pericardial effusion in dogs.
Authors: Refsum H , Jünemann M , Lipton M J , Skiöldebrand C , Carlsson E , Tyberg J V
Published: June 2011

We investigated the role of the pericardium in the mechanism of shifts in the left ventricular (LV) diastolic pressure-volume relation produced by changes in circulating blood volume and by pericardial effusion. Twelve closed-chest anesthetized dogs were instrumented with pericardial and pleural balloons and intracardiac catheters for pressure measurements. We measured the volumes of the pericardium and the left and right ventricles by computed tomography (CT), integrating the area of CT cross-sections measured at 1-cm intervals from the cardiac apex to the aortic arch. The volumes of the pericardium and the cardiac chambers were changed by infusing 40 and 80 ml of dilute contrast medium into the pericardial space, by bleeding, and by rapidly infusing saline intravenously. Pericardial effusions of 80 ml reduced mean right ventricular volumes to 59% of control, whereas LV volumes were less severely compromised (81% of control). Total pericardial volume and pressure increased. Intravenous saline infusions, which raised right atrial pressure 10-15 mm Hg, produced increases of this magnitude in pericardial pressure. This was also the magnitude of the upward displacement in the LV diastolic pressure-volume relation after infusion. However, LV diastolic transmural pressure-volume coordinates fell along a single curve. Similar behavior was observed for the right ventricular diastolic pressure-volume relation. Pericardial transmural pressure-volume curves were described. When cardiac volume was altered by volume load and pericardial effusion, acute shifts in the LV diastolic pressure-volume relation were caused by changes in pericardial pressure, which, in turn, corresponded to changes in pericardial volume.
Demonstration of training effect during chronic beta-adrenergic blockade in patients with coronary artery disease.
Authors: Pratt C M , Welton D E , Squires W G , Kirby T E , Hartung G M , Miller R R
Published: June 2011

Attenuation of exercise-induced increases in heart rate and cardiac output by chronic beta-adrenergic blockade has been thought to compromise benefit of exercise training in patients with coronary artery disease (CAD). To assess this important issue, 35 CAD patients were evaluated by a 3-month walk-jog-cycle training program: 14 patients received no beta blocker (group 1), 14 received propranolol, 30-80 mg/day (group 2), and seven patients received propranolol, 120-240 mg/day (group 3). The extent of CAD, resting heart rate before training blood pressure and VO2 max were similar (p = NS) in each group. The maximal exercise heart rate (mean +/- SD, 147 +/- 21 beats/min in group 1 vs 120 +/- 10 beats/min in group 2 and 115 +/- 12 beats/min in group 3 (both p less than 0.05 vs group 1). The VO2 max before training was 25 +/- 5.0 ml/kg/min in group 1 vs 23 +/- 3.2 ml/kg/min in group 2 and 26 +/- 2.8 ml/Kg/min in group 3 (all p = NS). Training consisted of three 1-hour periods per week at a heart rate of 70-85% of the maximal pretraining heart rate. In each group, VO2 increased (p less than 0.05) after training: group 1, 27%; group 2, 30%; group 3, 46%. The double product was unchanged after training (p = NS) in each group. These data indicate that substantial training effects may be achieved in CAD patients despite therapeutic doses of beta blockers and a reduced training HR. Thus, there appears to be no indication to reduce beta blockers in CAD patients engaged in cardiac rehabilitation.
Fluorescence microlymphography.
Authors: Bollinger A , Jäger K , Sgier F , Seglias J
Published: June 2011

Microneedles, 0.2 mm o.d., were connected to a microsyringe and mounted on a micromanipulator. Under microscopic control, 0.01 ml of a 25% solution of FITC-labeled dextran-40 or dextran-150 were injected into the subepidermis at the big toe near the nailfold or in the medial ankle region. Fluorescence intravital microscopy revealed a network of lymphatic microvessels. The comparison with recent anatomic studies reveals that the reticular network visualized by FITC-dextran corresponds to the network in the stratum papillare. In 20 healthy subjects lymphatic capillaries were detected in a restricted area on the lateral aspect of the big toe. In 10 patients with primary lymphedema, the dye expanded to almost the entire dorsal skin surface of the big toe. In two cases, enlarged and tortuous microvessels of pathologic shape were observed. Fluorescence microlymphography is a simple and nearly atraumatic approach for depicting the intravital anatomy of human skin lymphatic capillaries.
Acute and long-term effects of vasodilator therapy on resting and exercise hemodynamics and exercise tolerance.
Authors: Massie B M , Kramer B , Haughom F
Published: June 2011

The acute hemodynamic response to vasodilators in patients with chronic heart failure has been well characterized, but less is known about the long-term hemodynamic effects of vasodilator therapy. We measured hemodynamic variables at rest and during upright exercise in 11 patients during the initiation of therapy with oral hydralazine and sublingual isosorbide dinitrate and, in eight of these, after 3 months of continuous treatment. Marked initial increases in resting cardiac output and stroke volume and reductions in wedge pressure were sustained during chronic therapy. Similarly, the early improvement in exercise hemodynamic measurements persisted in most subjects. Exercise tolerance, quantified as the maximum duration of treadmill exercise, increased modestly (7.7 +/- 2.6 to 8.9 +/- 3.3 minutes, 0.05 less than p less than 0.10) after several days on vasodilators and further (10.2 +/- 3.7 minutes, p less than 0.01) during long-term treatment. The acute hemodynamic effects of vasodilator therapy at rest or during exercise did not correlate well with the changes in exercise tolerance. Our findings suggest that the combination of hydralazine and isosorbide dinitrate improves cardiac performance at rest and during exercise in patients with chronic heart failure and that this improvement persists during chronic therapy. In most patients, this hemodynamic improvement is accompanied by greater exercise tolerance.
Coronary arterial spasm in single coronary artery.
Authors: Yamamoto K , Koiwaya Y , Tajimi T , Inou T , Mitsutake A , Orita Y , Takeshita A , Nakamura M
Published: June 2011

A 48-year-old man developed severe chest pain and became unconscious. Coronary cineangiography revealed single coronary artery of the type L2b by Sharbaugh and White. Ergonovine, 0.2 mg i.v., produced coronary arterial spasm in the right coronary artery. This case suggests that coronary arterial spasm might be a cause of sudden death in patients with single coronary artery. However, an association of single coronary artery and coronary arterial spasm might be coincidental.
Effects of systemic hypertension on ischemic and nonischemic regional left ventricular function in awake, unsedated dogs after experimental coronary occlusion.
Authors: Roan P G , Buja M , Saffer S , Izquierdo C , Hagler H , Duke B , Hillis L D , Willerson J T
Published: June 2011

Hypertension and atherosclerotic coronary arterial obstruction frequently coexist in patients. However, the effect of increased aortic pressure on ischemic segmental dysfunction is not well understood. We studied the effects of aortic pressure increases on segmental left ventricular function during myocardial ischemia. Eighty-two dogs instrumented with three to six pairs of pulse-transit piezoelectric crystals were studied in an awake, unsedated state to measure segmental wall thickness. A pneumatic balloon occluder was positioned around the proximal left anterior descending artery (LAD). Thirty-three dogs underwent LAD occlusion and served as normotensive controls (group A). Group B dogs (n = 23) received a 6-hour infusion of phenylephrine (PE) beginning 5 minutes after LAD occlusion to increase aortic diastolic arterial pressure to 120-130 mm Hg; aortic pressure was then allowed to return to normal for the subsequent 18 hours. The eight dogs in group C received a 6-hour infusion of PE, but no coronary arterial occlusion was produced. In group D (n = 12), distal constriction of the thoracic aorta was maintained for 24 hours after LAD occlusion. Regional myocardial blood flow (RMBF) was measured with radioactive microspheres in six conscious dogs and both RMBF and intramyocardial PCO2 were measured in seven open-chest dogs to assess alterations in regional myocardial oxygen supply and demand. Segments of myocardium were arbitrarily grouped according to the amount of net systolic thickening (NET) present 5 minutes after LAD occlusion and before increasing aortic pressure: group 1 retained 67-100+% of control NET, group 2 0-67%, and group 3 less than 0% (paradoxic motion). In dogs receiving PE plus LAD occlusion and in dogs with aortic constriction and LAD occlusion, NET was transiently depressed in groups 1 and 2 compared with the normotensive cohort; 24 hours after occlusion, NET in groups 1, 2 and 3 did not differ significantly from that in the normotensive dogs. Systemic hypertension resulted in a significant increase in endocardial and midwall RMBF and, in seven open-chest dogs, decreased the intramyocardial accumulation of carbon dioxide after LAD occlusion. Increased aortic pressure in dogs without coronary occlusion produced reversible decreases in end-diastolic wall thickness, NET and LV dP/dt. Thus, the production of systemic hypertension with diastolic pressures of 110-120 mm Hg acutely or for 6 hours during evolving canine myocardial infarction does not appear to exert an important deleterious effect on myocardial oxygen supply and demand. However, 24 hours of mildly increased aortic pressure accentuates end-diastolic wall thinning in segments with paradoxic systolic motion and results in a failure of their return to control values at this period.
The effect of age on heart rate in subjects free of heart disease. Studies by ambulatory electrocardiography and maximal exercise stress test.
Authors: Kostis J B , Moreyra A E , Amendo M T , Di Pietro J , Cosgrove N , Kuo P T
Published: June 2011

To delineate the effects of true aging, undetected heart disease and deconditioning on heart rate, we performed 24-hour ambulatory electrocardiography and maximal exercise stress test on 101 subjects with normal hearts. The maximal heart rate recorded was 180 beats/min; the minimum was 35 beats/min. A distinct diurnal pattern was observed. With increasing age, a decrease of the maximal heart rate achieved during exercise stress test (r = 0.27, p = 0.05) or spontaneously recorded during the day (r = 0.41, p = 0.0005) or night (r = 0.24, p = 0.03) was observed. The resting and average heart rates were not affected by age. Older subjects had lower exercise tolerance (r = 0.41, p = 0.0001). Low exercise tolerance was associated with higher increments of heart rate for submaximal exercise levels (r = 0.0001) and lower maximal heart rates (r = 0.43, p - 0.008). These changes of heart rate with age are not due to undetected cardiac disease, because the subjects included in the study were meticulously screened by noninvasive and invasive means.
Stereoselective interaction of sulfinpyrazone with racemic warfarin and its separated enantiomorphs in man.
Authors: O'Reilly R A
Published: June 2011

Although serious hemorrhage during therapeutic coadministration of sulfinpyrazone and racemic warfarin occurs, no prospective studies have been done. In this study, single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects with and without oral sulfinpyrazone, 400 mg daily. Both the hypoprothrombinemia (p less than 0.001) and the plasma warfarin concentrations (p less than 0.05) were significantly augmented. To determine if this interaction was stereoselective, the experiments were repeated in the same subjects with R-and S-warfarin enantiomorphs. S-warfarin with sulfinpyrazone caused a highly significant augmentation of both the hypoprothrombinemia (p less than 0.001) and the plasma warfarin concentrations (p less than 0.001). R-warfarin with sulfinpyrazone did not significantly change the hypoprothrombinemia but significantly (p less than 0.05) reduced warfarin concentrations. Thus, sulfinpyrazone augmented the hypoprothrombinemia of racemic warfarin stereoselectively by reduced metabolic clearance of S-warfarin. Sulfinpyrazone and racemic warfarin are most dangerous when either drug is added to a stabilized regimen of the other drug.
Response of the systemic and pulmonary circulation to converting-enzyme inhibition (captopril) at rest and during exercise in hypertensive patients.
Authors: Fagard R , Bulpitt C , Lijnen P , Amery A
Published: June 2011

Twenty sodium-replete patients with hypertension were allocated either to a placebo or to a captopril treatment group. Each patient was investigated in rest-recumbent (RR) and rest-sitting (RS) positions and during an uninterrupted, graded, submaximal exercise test (up to the anaerobic threshold) before treatment, and with a similar protocol 75 minutes after treatment with captopril or placebo on the same morning. Captopril decreased brachial intraarterial pressure by 7/4 mm Hg at RR, by 16/10 mm Hg at RS, and by 19/10 mm Hg during exercise (p less than 0.001), based on a decrease of systemic vascular resistance (p less than 0.001). Slight increases of cardiac output and of heart rate were noted at rest; cardiac output was not significantly affected during exercise, but the increase of heart rate of 2.4 beats/min was significant (p less than 0.01). Captopril decreased pulmonary artery (p less than 0.05) and capillary wedge pressures (p less than 0.001), with unchanged pulmonary vascular resistance. The data indicate that the action of captopril is characterized by arteriolar and possibly venous dilatation both at rest and during exercise. Pulmonary vascular resistance, however, is not affected.
The effects of nifedipine on myocardial blood flow and contraction during ischemia in the dog.
Authors: Weintraub W S , Hattori S , Agarwal J B , Bodenheimer M M , Banka V S , Helfant R H
Published: June 2011

Nifedipine has been proposed as an agent to preserve viability and function of ischemic myocardium. We studied 23 open-chest dogs that underwent carotid-to-left anterior coronary artery perfusion with flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the ischemic and nonischemic endocardium. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to 25 mm Hg diastolic perfusion pressure. Ten dogs received intracoronary nifedipine, 10 micrograms, and 13 dogs received i.v. nifedipine, 3 micrograms/kg/min. Nifedipine resulted in an increase in segmental shortening in both groups, but nonischemic zone shortening did not change in either group. Nifedipine did not affect myocardial blood flow in the ischemic zone, but increased flow in the nonischemic zone in the group that received i.v. nifedipine. Thus, nifedipine appears to have a direct beneficial effect on ischemic myocardium.
Late survival and symptoms after repair of tetralogy of Fallot.
Authors: Katz N M , Blackstone E H , Kirklin J W , Pacifico A D , Bargeron L M
Published: June 2011

The long-term results of 414 patients who underwent repair of tetralogy of Fallot between 1967 and 1977 were studied and correlated with the results of others. There were nine late deaths (8-year actuarial survival 95.8%). Six of the deaths wee directly related to the malformation or its treatment. Eight patients (2.4%) required reoperation. Ten patients (4.8%) had arrhythmic symptoms. Eight (3.1%) had congestive heart failure that required treatment. The risk factors associated with late events of all types, including death, were: older age at repair, a high mean ratio of peak systolic right-to-left ventricular pressures (PLV/RV) immediately after repair, and the presence of a Potts anastomosis. Neither a transannular patch nor a previous Blalock-Taussig or Waterson anastomosis was an incremental risk factor. Bacterial endocarditis was not observed. Three hundred seven patients underwent repair primarily or after a single Blalock-Taussig or Waterston shunt and had a PRV/LV of 0.85 or less after repair. Among these selected patients, the actuarial survival was 98.1%, which is still lower than that for the general population (p = 0.12), and freedom from events was 95.9%. Late after repair, PRV/LV was lower by 6 +/- 28% (+/- SD) than PRV/LV immediately after repair (p = 0.03) in the 33 restudied patients with such data. The higher the PRV/LV immediately after repair, the greater the percent reduction.
Influence of heart rate and inhibition of autonomic tone on the QT interval.
Authors: Ahnve S , Vallin H
Published: June 2011

To evaluate whether heart-rate-induced changes of the QT interval are dependent on autonomic tone, we studied 13 healthy subjects, mean age 67.5 years. The maximal uncorrected QT from leads I, II, V1 and V6 was determined during atrial pacing at 90 beats/min and 130 beats/min before and after i.v. administration of propranolol, 0.1 mg/kg, and atropine, 0.02 mg/kg. Significant reductions (p less than 0.01) of QT were induced by the paced increases in heart rate before drugs (10%), after propranolol (10%) and after the combination of atropine and propranolol (9%). Propranolol caused no significant change in the QT interval when heart rate was held constant by pacing. In contrast, atropine produced rate-independent reductions of QT interval (5%) in subjects with beta-adrenergic blockade (p less than 0.05). Bazett's formula for heart-rate correction of the QT interval (QTc) was not applicable for atrial overdrive pacing, as it gave proportionately longer QTc values at higher heart rates. These results show that heart rate is a major determinant of the duration of the QT interval and that paced changes in heart rate induce QT-interval responses that are essentially uninfluenced by autonomic tone. The rate-dependent effect of the QT interval produced by elimination of cholinergic tone suggests a direct influence of cholinergic activity on the repolarization of ventricular myocardium.
Clinical classification of cardiac deaths.
Authors: Hinkle L E , Thaler H T
Published: June 2011

One hundred forty-two deaths among 743 men ages 50 - 65 years who had been examined and followed 5 - 10 years were investigated and classified on the basis of clinical information from medical and non-medical observers, ECGs and autopsies. A classification based on the condition of the circulation immediately before death appears to be most relevant to studies of sudden death. In 58% of the cases, the subjects collapsed abruptly and his pulse ceased without prior circulatory collapse (arrhythmic death); in 42%, the pulse ceased only after the peripheral circulation had collapsed (deaths in circulatory failure). Thirty-three percent of arrhythmic deaths and 10% of deaths in circulatory failure occurred in a setting of clinical evidence of acute ischemic heart disease (p less than 0.005). Forty-five percent of arrhythmic deaths were preceded by chronic congestive heart failure without circulatory collapse. Ninety-three percent of final illnesses that lasted less than 1 hour ended in arrhythmic deaths; 74% lasted more than 1 day ended in deaths in circulatory failure (p less than 0.001). Eighty-eight percent of deaths that occurred outside of the hospital were arrhythmic; 71% of deaths that occurred in the hospital were deaths in circulatory failure (p less than 0.001). Ninety percent of deaths in which the primary cause of the final illness was heart disease were arrhythmic; 86% of deaths in which the primary cause was other than heart disease were deaths in circulatory failure (p less than 0.001). Ninety-one percent of deaths precipitated by an acute cardiac event were arrhythmic; 98% precipitated by acute respiratory obstruction, hemorrhage, infection, stroke or other noncardiac events were deaths in circulatory failure (p less than 0.001).
Hemodynamic effects of hydralazine in infants with a large ventricular septal defect.
Authors: Beekman R H , Rocchini A P , Rosenthal A
Published: June 2011

To evaluate the effects of acute afterload reduction, hydralazine, 0.2 mg/kg, was administered at cardiac catheterization to seven infants who had a large ventricular septal defect (VSD). The infants were 2.5 - 11 months old (mean 5.1 months). Before and 5, 15, 25 and 35 minutes after hydralazine, aortic, pulmonary capillary wedge, pulmonary artery, right atrial and superior vena caval pressures and saturations, heart rate and oxygen consumption were measured. Hemodynamic effects were noted after 5 minutes but were most pronounced 35 minutes after hydralazine. Prehydralazine baseline data were therefore compared with values 35 minutes after hydralazine. Pulmonary flow did not changes, but systemic flow increased significantly (4.5 +/- 0.2 to 6.7 +/- 0.5 liters/min/m2 [mean +/- SEM], p less than 0.001). The pulmonary-to-systemic flow ratio decreased by 32% (3.4 +/- 0.4 to 2.3 +/- 0.2, p less than 0.001) and the absolute left-to-right shunt decreased by 24% (10.8 +/- 1.3 to 8.2 +/- 1.2 liters/min/m2, p less than 0.01). Hydralazine caused a significant decrease in systemic resistance (13.9 +/- 0.7 to 9.5 +/- 0.7 U, p less than 0.001). Pulmonary resistance, aortic, pulmonary artery and pulmonary capillary wedge pressures, heart rate and oxygen consumption did not change after hydralazine. Right atrial pressure decreased slightly (4.0 +/- 0.6 to 2.4 +/- 0.6 mm Hg, p less than 0.05). In conclusion, hydralazine caused a significant increase in systemic blood flow and a significant decrease in both pulmonary-to-systemic flow ratio and absolute left-to-right shunt in seven infants with a large VSD. These effects appear to be related to the decrease in systemic resistance that occurred with hydralazine. Although limited to the acute setting, these findings suggest that hydralazine may be beneficial in the management of infants with a large VSD.
Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance.
Authors: Flaherty J T , Weisfeldt M L , Bulkley B H , Gardner T J , Gott V L , Jacobus W E
Published: June 2011

Phosphorus-31 nuclear magnetic resonance (31P NMR) can estimate tissue intracellular pH as well as the content of high-energy phosphate metabolites in isolated perfused hearts. We used 31P NMR to examine mechanisms associated with the recovery of ventricular function in hearts subjected to global ischemia and reperfusion, with special emphasis on intracellular pH, a previously unreported variable. Single-dose and multiple-dose administration of a hyperkalemic cardioplegic solution were compared with hypothermia alone in 18 isolated perfused rabbit hearts. Hearts in group 1 were subjected to 24 degrees C hypothermia during 60 minutes of global ischemia; group 2 hearts received a single injection of 37-mM KCL cardioplegic solution at 10 degrees C at the onset of ischemia; and group 3 hearts received a similar initial cardioplegic injection followed by two subsequent 24 degrees C injections at 20-minute intervals during the ischemic period. Using an intraventricular balloon, maximal dP/dt provided a quantitative index of left ventricular performance before and after ischemia. Return of ventricular function expressed as a percentage of control was 54 +/- 11% for group 1, 84 +/- 6% for group 2, and 101 +/- 18% for group 3. Differences in the rate of development of intracellular acidosis were noted during the 60-minute ischemic period. Intracellular pH fell to 6.09 +/- 0.12 in group 1, 6.31 +/- 0.09 in group 2, an 6.79 +/- 0.03 in group 3. In all three groups intracellular pH returned to control (pH 7.20) within 10 minutes of reflow. The metabolic correlates of functional recovery appeared to be the tissue content of ATP at the end of ischemia and after reflow. ATP content at the end of ischemia was 22 +/- 2% of control in group 1 hearts, 31 +/- 4% in group 2 and 64 +/- 2% in group 3. After 45 minutes of reperfusion, ATP levels recovered to 33 +/- 9% of control in group 1, to 71 +/- 9% in group 2 and to 86 +/- 6% in group 3. Although there were no differences between groups in the content of creatine phosphate after 60 minutes of ischemia, the rates of creatine phosphate decline were dissimilar. Further, during the early reflow period, a marked overshoot in tissue creatine phosphate was detected, especially in groups 1 and 2. Histologic damage assessed by light microscopy correlated with the metabolic data, confirming that multidose cardioplegia provided the best preservation of cellular morphology. These results demonstrate that the magnitude of intracellular acidosis and the associated increase in inorganic phosphate correlate inversely with recovery of postischemic ventricular structure and function. ATP, but not creatine phosphate, content correlates with return of contractile performance after reperfusion. The overshoot in creatine phosphate during early reperfusion might impede optimal restoration of ATP content and, as a result, optimal recovery of cell functions.
Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man.
Authors: Packer M , Meller J , Medina N , Yushak M , Smith H , Holt J , Guererro J , Todd G D , McAllister R G , Gorlin R
Published: June 2011

The administration of verapamil to patients receiving beta-adrenergic blocking drugs is reported to produce adverse circulatory reactions, but a systematic investigation of this potential drug interaction has not been performed in man. We administered 40-, 80- and 120-mg doses of verapamil orally to 15 patients with angina pectoris who were receiving high doses of propranolol or metoprolol. Verapamil produced dose-dependent decreases in cardiac performance: with 120 mg, cardiac index decreased by 0.38 l/min/m2, stroke volume index decreased by 2.8 ml/beat/m2 and heart rate decreased by 6 beats/min, associated with increases in pulmonary capillary wedge (2.2 mm Hg) and mean right atrial pressures (1.7 mm Hg) (all p less than 0.01); two patients had marked, but asymptomatic, hypotensive reactions. In contrast, repeat administration of 120-mg doses of verapamil 24--30 hours after withdrawal of beta blockade produced no significant cardiodepressant effects despite significantly higher plasma levels of verapamil than during propranolol therapy (383.1 vs 205.1 ng/ml, p less than 0.01). In conclusion, verapamil produces significant negative inotropic and chronotropic effects in patients treated with beta-adrenergic antagonists; combination therapy should therefore be used with caution in patients with angina pectoris.
Factors in predicting blood pressure change.
Authors: Sparrow D , Garvey A J , Rosner B , Thomas H E
Published: June 2011

A total of 1166 male participants (ages 23--80 years) of the Normative Aging Study who had baseline blood pressure less than 140/90 mm Hg were followed prospectively for 10 years. Blood pressures were taken at 5- and 10-year follow-up examinations. Multiple linear regression analysis indicated that baseline levels of systolic pressure, hematocrit, subscapular skinfold thickness and age were significant predictors of systolic pressure change during the follow-up period. Baseline levels of diastolic pressure, hematocrit, and body mass index were significant predictors of diastolic pressure change. Multiple logistic regression analysis revealed that only baseline blood pressure and hematocrit were significant predictors of subsequent blood pressure elevation to more than 159 mm Hg systolic or 94 mm Hg diastolic. Although the mechanisms by which hematocrit and body build affect blood pressure are unknown, these results suggest that identifying hypertension-prone subjects and delaying or preventing hypertension may be possible.
The potentiation of warfarin anticoagulation by amiodarone.
Authors: Hamer A , Peter T , Mandel W J , Scheinman M M , Weiss D
Published: June 2011

The potentiation of the anticoagulant effect of sodium warfarin by amiodarone is reported in 10 patients. Amiodarone appears to augment the depression of vitamin K-dependent coagulation factors caused by warfarin by an uncertain mechanism, and may lead to serious bleeding. The maintenance dose of warfarin should be halved when amiodarone and warfarin are prescribed together.
Aggravation and provocation of ventricular arrhythmias by antiarrhythmic drugs.
Authors: Velebit V , Podrid P , Lown B , Cohen B H , Graboys T B
Published: June 2011

Antiarrhythmic drugs may aggravate or even induce ventricular arrhythmias. This type of adverse reaction is becoming more prevalent as the use of antiarrhythmic agents becomes more widespread. In a retrospective analysis of antiarrhythmic drug action, a worsening of arrhythmia was observed in 80 of 722 (11.1%) antiarrhythmic drug tests in 53 of 155 patients being treated for ventricular tachyarrhythmias. Aggravation of arrhythmias was defined by occurrence of a fourfold increase in the frequency of ventricular premature complexes, a 10-fold increase in repetitive forms, or the first emergence of sustained ventricular tachycardia coincident with time course of action of the particular drug under study. Such aggravation was noted with each of nine drugs tested: quinidine, procainamide, disopyramide, propranolol, metoprolol, aprindine, mexiletine, tocainide and pindolol. The frequency of this complication for a specific drug ranged from 5.9-15.8%. Blood drug concentrations were consistently in the therapeutic range. A study of the variability of ventricular arrhythmia during 48-hour Holter monitoring and exercise stress testing in no instance showed arrhythmia enhancement commensurate with that defining aggravation. Our data suggest that this potentially serious complication is not readily predictable and requires a systematic approach to antiarrhythmic drug testing before a patient is prescribed a long-range maintenance program.
Evidence that hospital care for acute myocardial infarction has not contributed to the decline in coronary mortality between 1973-1974 and 1978-1979.
Authors: Goldman L , Cook F , Hashimotso B , Stone P , Muller J , Loscalzo A
Published: June 2011

To investigate whether the reported 17% decline in the national rates of acute ischemic heart disease mortality between 1973 and 1978 was attributable to decreased in-hospital mortality for patients with acute myocardial infarction (MI), we surveyed all 63 acute care hospitals in the Boston, Massachusetts, area. Compared with 1973-1974, more 1978-1979 MI patients were admitted to hospitals in metropolitan Boston, and especially to the five university teaching hospitals. Between 1973-1974 and 1978-1979, hospital admission rates decreased for younger patients and increased for older patients, but overall admission rates were almost identical. In-hospital mortality rates from acute MI did not change significantly in any age group. Because overall MI mortality was declining while in-hospital MI mortality was unchanged, the proportion of acute MI deaths that occurred inside the hospital increased from about 30% to about 40%. Although current hospital care undoubtedly benefits many individual patients, this study suggests that improvements in the in-hospital care of acute MI patients are a major explanation for nationwide mortality trends between 1973 and 1978.
Sensitivity of end-systolic pressure-dimension and pressure-volume relations to the inotropic state in humans.
Authors: Borow K M , Neumann A , Wynne J
Published: June 2011

The value for the slope of the left ventricular (LV) end-systolic pressure-dimension and pressure-volume relations has been proposed as a quantitative measure of the LV inotropic state. This measure of LV inotropic state is attractive because it is independent of preload and incorporates afterload. To investigate the sensitivity of the slope of these relations to alterations in contractile state, 10 normal subjects were studied using M-mode echocardiographic, phonocardiographic and indirect carotid pulse recordings during infusion of methoxamine to alter end-systolic pressure and during infusion of dobutamine (5 micrograms/kg/min) to increase LV inotropic state. Heart rate was maintained within a narrow range for each subject. End-systolic volume was calculated from end-systolic echocardiographic dimension by standard methods. End-systolic pressure was estimated from the dicrotic notch pressure determined from a calibrated carotid pulse recording; peak systolic pressure was also measured. Regardless of the method of approximating end-systolic pressure, the positive inotropic intervention caused a leftward shift in the end-systolic pressure-dimension and pressure-volume lines. With the dobutamine infusion, the value for the slope of the end-systolic pressure-dimension relation increased by 25% (range 16-46%, p less than 0.001), while the slope of the end-systolic pressure-volume relation increased by 55% (range 37-85%, p less than 0.001). In all cases, the curves were linear and became steeper with the positive inotropic intervention. In contrast, the value of the slope of the peak systolic pressure-end-systolic dimension relation showed a variable response to the dobutamine infusion (mean change 13%, range -77% to 73%; NS). Although the position of the peak systolic pressure-end-systolic dimension curve is consistently shifted with an alteration in inotropic state, the values of the slope of these curves are not reliable indicators of change in LV contractility. The values for the slope of the line relating end-systolic pressure (estimated by dicrotic notch pressure) to end-systolic dimension or volume, however, are highly sensitive to a change in inotropic state in human subjects.
Effect of perioperative myocardial infarction on late survival in patients undergoing coronary artery bypass surgery.
Authors: Namay D L , Hammermeister K E , Zia M S , DeRouen T A , Dodge H T , Namay K
Published: June 2011

From the Seattle Heart Watch angiography registry, the baseline characteristics and late survival of 77 patients who sustained operative infarction (new Q waves) with myocardial revascularization were compared with 1790 patients who underwent coronary artery bypass without perioperative infarction. With the exception of coronary collateral vessels, which were less frequently seen in the patients with perioperative infarction, no baseline or operative characteristic distinguished between the two groups. Late survival was clearly adversely affected by perioperative infarction. Five-year survival was 76% in patients with perioperative infarction, compared with 90% in those with no perioperative infarction.
Anatomic effects of cryoablation of the atrioventricular conduction system.
Authors: Ohkawa S , Hackel D B , Mikat E M , Gallagher J J , Cox J L , Sealy W C
Published: June 2011

Because of the value of cryoablation of the atrioventricular (AV) conduction system in treatment of refractory cardiac rhythm disorders, the anatomic effects of cryoablation on the cardiac conduction system must be defined. In this report we summarize studies done on four patients who had intractable recurrent supraventricular tachyarrhythmias or or refractory atrial flutter-fibrillation. They were treated by cryoablation of the AV conduction system and died 8-360 days postoperatively. Serial sections of the AV conduction system were studied. Cryoablation produced lesions that completely destroyed most of the AV node in three cases, the penetrating portion of the His bundle in all four cases, and the branching portion of the His bundle in two cases. The right bundle branch was not involved markedly in any case. The lesions were discrete and sharply delimited; the patient who died 8 days postoperatively had hemorrhage, necrosis and slight inflammatory infiltrate; patients who survived for 49-360 days showed collagen deposition. The AV nodal artery and its branches showed slight to marked intimal thickening in three cases. Small, partly organized thrombi were present just behind the tricuspid valve in two patients. We conclude that cryoablation of the AV conduction system produced discrete cardiac lesions that did not markedly damage the tricuspid valve or aorta.
Comparison of postpacing and exercise-induced myocardial dysfunction during collateral development in conscious dogs.
Authors: Kumada T , Gallagher K P , Battler A , White F , Kemper W S , Ross J
Published: June 2011

In 10 conscious dogs, a model was developed for studying regional contractile responses in a coronary collateral-dependent bed. Regional myocardial function was compared after terminating a maximum paced rate of 240 beats/min maintained for 3 minutes (postpacing period) with that during telemetry-monitored exercise at comparable heart rates (average 252 +/- 34 beats/min, duration 2.4 minutes) at different times during collateral development. Ultrasonic dimension gauges were used to measure control and ischemic segment (CS and IS) lengths and ischemic zone regional wall thickness (IW). An ameroid constrictor and a Doppler flow probe were placed around the left circumflex coronary artery, and pacing electrodes were sutured to the right ventricle. An average of 23 days postoperatively, coronary obstruction was complete. Studies at that time showed that percent shortening (% delta L) of IS and percent wall thickening (% delta W) of IW decreased after pacing to 57% and 35% of control, respectively, and during exercise to 37% of control. One week later (average 30 days postoperatively), significant depression of regional function no longer occurred postpacing. However, exercise at a comparable heart rate still provoked regional dysfunction in the collateral-dependent zone: Both IS% delta L and IW% delta W decreased to 51% of control. Regional function at rest did not differ during these studies. Thus, the effectiveness of the postpacing response for detecting limited collateral reserve was eliminated by further collateral development, but regional myocardial dysfunction during exercise stress served to detect ischemia despite increased collateral circulation.
An experimental model for congestive heart failure after encephalomyocarditis virus myocarditis in mice.
Authors: Matsumori A , Kawai C
Published: June 2011

Severe myocarditis was induced in inbred BALB/c mice inoculated with the M variant of encephalomyocarditis (EMC) virus. The mortality rate was maximal on the fourth day, then decreased gradually, but increased again between the eleventh and fourteenth days. Gross myocardial lesions were seen on the surface of the ventricles in 62 of 125 mice (49.6%) after the fifth day. These myocardial lesions were observed more frequently in the dead mice (46 of 49, 93.9%). Cavity dimensions and wall thickness were measured in two groups of mice with myocarditis. On days 5-7, the cavity dimensions of the right (RV) and left (LV) ventricles in inoculated mice (0.92 +/- 0.51 mm and 1.21 +/- 0.18 mm, respectively) were significantly larger than those in controls (RV 0.54 +/- 0.17, LV 1.01 +/- 0.15; p less than 0.05). The wall thickness of the RV (0.46 +/- 0.09, controls 0.64 +/- 0.11; p less than 0.001) and the LV (0.97 +/- 0.13, controls 1.12 +/- 0.19; p less than 0.05) was significantly decreased. On days 8-14, dilatation of the LV was more pronounced (1.48 +/- 0.37, p less than 0.005) than during days 5-7, and the interventricular septum was also thinner. Pleural effusion, ascites and congestion of the lungs and liver were noted, and death seemed due to congestive heart failure. This study is the first documentation of congestive heart failure after viral infection is an experimental animal.
The sinus node in sudden infant death syndrome.
Authors: Kozakewich H P , McManus B M , Vawter G F
Published: June 2011

The sinus node (SN) was examined histologically in 30 infants diagnosed with sudden infant death syndrome (SIDS) and in 18 age-matched controls who died of known causes. Location, size and organization of the SN did not differ significantly in the two groups Petechiae involved the SN region in 20% of SIDS and 17% of control infants and probably do not represent a primary event. In three SIDS infants (10%), intimal lesions reduced the lumen of the intranodal SN artery by 63-83% in cross-sectional area. These resembled the intimal thickenings frequently observed in main epicardial coronary arteries of infants. Whether the vascular alterations in these three cases had adverse effects upon SN function is unknown.