bluuebunny/crossref_metadata_2025 huggingface dataset:
Contractile reserve and left ventricular function in regional myocardial ischemia in the dog.
Authors: Yoran C , Sonnenblick E H , Kirk E S
Published: June 2011

Contractile activity remaining in a region made ischemic by acute occlusion of the left anterior descending coronary artery (LAD) was assessed in dogs relative to its role in maintaining left ventricular (LV) function. Compensatory increases in contractility of normal myocardium were eliminated by treating all dogs with reserpine (3 mg/kg) to deplete their catecholamine stores. LV function was determined by measuring stroke volume while increasing the LV filling pressure with a shunt from the aorta to left atrium. Heart rate and mean aortic pressure were kept constant. LV function was studied after occlusion of the LAD alone and after the selective infusion of potassium chloride (1 mEq/ml) into the LAD to raise the regional extracellular potassium concentration to 30 mEq/ml. The reduction in LV function induced by LAD ligation was less than the reduction caused by abolishing contraction in the entire zone supplied by the LAD with infusion of potassium. The totally cardioplegic zone induced by potassium amounted to 20.3-39.8% of the LV mass. At an LV end-diastolic pressure of 12 mm Hg, stroke volume (SV) was reduced in proportion to the size of the cardioplegic zone: -SV (% volume) = -1.55% (% of LV mass) + 120.1 (r = -0.69, p less than 0.005). Thus, a dyskinetic zone of 35% of the left ventricle reduced stroke volume by 34% when adrenergic compensation was blocked. We conclude that residual transmural contractility exists in the ischemic region of myocardium subserved by an obstructed LAD and contributes significantly to LV function.
Mechanisms governing the postural response and baroreceptor abnormalities in chronic congestive heart failure: effects of acute and long-term converting-enzyme inhibition.
Authors: Cody R J , Franklin K W , Kluger J , Laragh J H
Published: June 2011

We assessed the hemodynamic and hormonal response to tilt and the baroreceptor response in 12 patients in sinus rhythm with severe chronic congestive heart failure. We also assessed the response to acute (n = 12) and chronic (n = 8) converting-enzyme inhibition with captopril. The control tilt was characterized by high cardiac filling pressures, absence of significant peripheral pooling and apparent absence of afferent stimuli for hemodynamic and hormonal response. After acute captopril, the hemodynamic response to tilt was improved, but not normalized. The chronic response was characterized by the absence of a reflex increase of systemic vascular resistance on tilt despite peripheral pooling. Five patients developed orthostatic hypotension, but responded to acute infusion of 0.9% sodium chloride. Efferent sympathetic activity (response to cold pressor) was abnormal during the control study, but indistinguishable from normal subjects by the time of chronic captopril therapy. This paralleled an improved responsiveness of plasma catecholamines during chronic tilt. The Valsalva maneuver remained abnormal. There was a distinct absence of the normally anticipated heart rate increase on tilt, suggesting a parasympathetic abnormality.
Arterial oxygenation and arterial oxygen transport in chronic myocardial failure at rest, during exercise and after hydralazine treatment.
Authors: Rubin S A , Brown H V , Swan H J
Published: June 2011

Arterial oxygen transport (cardiac output x arterial oxygen content) may be decreased in heart failure. We studied the determinants of arterial oxygen transport in 15 patients with chronic, severe myocardial failure at rest and during cycle ergometry. During control therapy at rest, arterial oxygen tension was normal (81 +/- 8 mm Hg, mean +/- SD) and increased slightly during exercise (90 +/- 14 mm Hg). During hydralazine therapy at rest, arterial oxygen tension was slightly higher (87 +/- 9 mm Hg) and also increased during exercise (92 +/- 15 mm Hg). Hydralazine did not increase arterial oxygen tension (0.10 greater than p greater than 0.05), but exercise did (p less than 0.02). Arterial oxygen saturation and content were normal and did not change under any condition or treatment. During control therapy at rest, arterial oxygen transport was low (313 +/- 74 ml/min . m2) and remained abnormally low during exercise (434 +/- 124 ml/min . m2). During hydralazine therapy, arterial oxygen transport was higher at rest (457 +/- 100 ml/min . m2) and during exercise (577 +/- 131 ml/min . m2). Hydralazine increased arterial oxygen transport (p less than 0.01) because it increased stroke volume at rest and during exercise, but it did not change arterial oxygenation. Arterial oxygenation is normal in chronic heart failure patients at rest and during exercise. Hydralazine increases cardiac output and arterial oxygen transport without changing arterial oxygenation.
Pharmacokinetic significance of serum reverse T3 levels during amiodarone treatment: a potential method for monitoring chronic drug therapy.
Authors: Nademanee K , Singh B N , Hendrickson J A , Reed A W , Melmed S , Hershman J
Published: June 2011

We studied the antiarrhythmic effects of amiodarone, 600-1400 mg/day, in 18 patients with refractory arrhythmias, and related to drug efficacy and side effects to serum levels of T4, reverse T3 (rT3) and the QTc interval. In the 11 patients with ventricular arrhythmias, premature complexes were reduced by 90-98%, and complex ectopy and runs of ventricular tachycardia were abolished; in the seven patients with paroxysmal atrial flutter, there were no recurrences on stable drug therapy. The QTc lengthened by 11.6% (p less than 0.01), T4 increased by 31.6-63.3% (p less than 0.001) and rT3 increased by 82.9-176.8% (p less than 0.001) as a function of dose and duration of amiodarone therapy. A close correlation was found between rT3 (normal up to 50 ng/dl) and drug efficacy and some of the drug side effects; arrhythmia suppression occurred at levels of 55-100 ng/dl, and some of the known side effects at levels of 100-110 ng/dl. When amiodarone was stopped in nine patients, the changes in QTc, T4 and rT3 regressed toward normal and arrhythmia recurred in eight 2-20 weeks (mean 7.4 weeks) and when rT3 levels fell below 55 ng/dl; arrhythmia resuppression was achieved 3-28 days (mean 11 days) after resumption of amiodarone therapy. The indirect therapeutic half-life of amiodarone in seven patients, computed from the semilogarithmic plots of plasma rT3 after cessation of amiodarone therapy, ranged from 25 to 55 days (mean 35 days). The data suggest that rT3 levels may be useful in monitoring the efficacy and certain side effects of amiodarone.
Plasma catecholamines, platelet aggregation and associated thromboxane formation after physical exercise, smoking or norepinephrine infusion.
Authors: Siess W , Lorenz R , Roth P , Weber P C
Published: June 2011

To study the possible role of catecholamines in platelet activation, platelet aggregation stimulated by ADP, collagen, arachidonic acid and L-epinephrine, thromboxane B2 (TXB2) formation and plasma levels of catecholamines and renin were studied in healthy men both before and after 6 days of propranolol treatment (40 mg three times daily) under control conditions and during sympathoadrenergic stimulation by physical exercise (200 W) or smoking. Exercise markedly increased plasma norepinephrine from 128 +/- 28 to 998 +/- 418 pg/ml (+/- SD), and plasma renin activity from 1.0 +/- 0.5 to 4.2 +/- 1.8 ng AI/ml . hour. Smoking predominantly increased plasma epinephrine, from 47 +/- 25 to 154 +/- 76 pg/ml. Propranolol did not consistently influence these variables, but blunted the circulatory response to exercise and smoking. Despite the marked increases of plasma catecholamines after both stimuli with and without beta blockade, platelet aggregation stimulated by ADP, 1-epinephrine, collagen and arachidonic acid and associated TXB2 formation were not enhanced. Moreover, as already suggested by a trend toward reduced aggregability in these settings, plasma norepinephrine levels in the same range (745 +/- 368 pg/ml) due to infusion (5 micrograms/min) significantly reduced platelet aggregation with low-dose collagen (0.25-0.75 micrograms/ml), I-epinephrine (0.2-1.0 microM) and ADP (0.5-1.5 microM). These data do not support a role of endogenous catecholamines in initiating platelet activation and TXB2 formation.
Aneurysms of the coronary arteries in Kawasaki disease. An angiographic study of 30 cases.
Authors: Onouchi Z , Shimazu S , Kiyosawa N , Takamatsu T , Hamaoka K
Published: June 2011

Thirty patients with coronary aneurysms associated with Kawasaki disease underwent coronary arteriography. Of 53 aneurysms, five were saccular, 24 sacculofusiform, 19 fusiform and five tubular. When tubular aneurysms were included in the fusiform type, the incidence of each configuration in the right coronary artery was almost the same as that in the left coronary artery. The left anterior descending coronary artery had the most aneurysms, followed by the right coronary, left main and circumflex arteries. Right coronary aneurysms always involved the bifurcation or the region from which a branch vessel arose; 13 of 31 left coronary aneurysms did not involve the bifurcation.
Quantitative effect of early coronary artery reperfusion in baboons. Extent of salvage of the perfusion bed of an occluded artery.
Authors: Geary G G , Smith G T , McNamara J J
Published: June 2011

We examined the extent to which ischemic myocardium was salvaged by reperfusion using a method that allowed expression of the volume of infarction as a percentage of the volume of the perfusion bed of the occluded artery (region at risk of infarction). In eight baboons, the left anterior descending coronary artery (LAD) was occluded for 2 hours, after which perfusion was restored. A control group of eight baboons underwent an identical protocol, but perfusion was not restored. Twenty-four hours after occlusion, microvascular dyes were injected into the LAD and adjacent arteries to delineate the perfusion bed of the occluded artery. The volume of infarction and volume of the perfusion bed were determined planimetrically. The mean percentage of the perfusion bed infarcted in the control baboons was 94.2 +/- 3.5% and 50.1 +/- 5.8% in the reperfused baboons. Hence, the mean percentage of the perfusion bed infarcted was reduced by 44.1% in the reperfused group compared with the control group (p less than 0.001). In reperfused baboons, hemorrhage occurred in the region of infarction but did not result in infarct extension. We conclude that reperfusion after 2 hours of coronary occlusion results in substantial salvage of ischemic myocardium in the baboon.
Effects of oral disopyramide phosphate on induction and sustenance of atrioventricular reentrant tachycardia incorporating retrograde accessory pathway conduction.
Authors: Kou H C , Hung J S , Lee Y S , Wu D
Published: June 2011

We performed electrophysiologic studies before and after oral administration of disopyramide phosphate, 200 mg every 6 hours, in 20 patients with atrioventricular (AV) reentrant tachycardia using a retrogradely conducting accessory pathway. Disopyramide markedly depressed retrograde accessory pathway conduction by increasing the mean ventricular paced cycle length that produced ventriculoatrial block (less than or equal to 287 +/- 4 to greater than or equal to 392 +/- 22 msec, p less than 0.01); it also depressed antegrade normal pathway AV conduction by increasing the atrial paced cycle length that produced AV block (287 +/- 9 to 328 +/- 7 msec, p less than 0.01). In 14 patients, tachycardia could not be induced or sustained after disopyramide phosphate. In 13 patients, this reflected depression of the retrograde limb with either absence of atrial echoes (nine patients) or induction of nonsustained tachycardia that terminated after the QRS complex (four patients), and in one, it reflected depression of the antegrade limb with induction of a single atrial echo not followed by a QRS response. In six patients, sustained tachycardia could still be induced after disopyramide. Oral disopyramide phosphate is effective in preventing induction of sustained AV reentrant tachycardia in most patients. This effect is achieved by depression of the retrograde limb of the reentrant circuit.
Lewis A. Conner Memorial Lecture. Choices that must not be made.
Authors: Remington R D
Published: June 2011

Throughout our professional lifetimes, we are conditioned by the need to choose; among careers, among treatments for our patients, among health habits and lifestyles. After detailing the extent to which a choice-making orientation has dominated our lives, our society, our health system, our science, this paper describes areas in which it is crucial that choices not be made. These include the choice between basic and applied research, between targeted and investigator-initiated research, between prevention and treatment of cardiovascular disease, and between the need to know (research on mechanisms of disease) and the need to take action (intervention in the individual and the community to control disease). In each of these areas, a decision to emphasize either alternative at the expense of the other is undesirable and defeats the basic goals of understanding and controlling heart and vascular disease. In discussing these sets of alternatives, the three major cardiovascular risk factors are discussed: cigarette smoking, high blood pressure and diet. Examples are chosen from research investigations on risk, intervention, treatment, prevention and community control.
Effects of a calcium-channel antagonist on large and small coronary arteries in conscious dogs.
Authors: Vatner S F , Hintze T H
Published: June 2011

The effects of i.v. nifedipine, 20 micrograms/kg, on left ventricular (LV) pressure, dP/dt, aortic pressure, heart rate, LV diameters, cardiac output, coronary blood flow and left circumflex coronary arterial diameter, and calculations of late diastolic coronary and total peripheral resistances and left circumflex coronary cross-sectional area were examined in 11 conscious dogs. In dogs with spontaneous rhythm, nifedipine induced an early, transient response characterized by hypotension and peak increases in coronary blood flow and decreases in total peripheral and late diastolic coronary vascular resistances. The peak effects on large coronary arteries were observed 2--5 minutes later, when mean arterial pressure was only 8.2 +/- 1.6 mm Hg below control and LV end-diastolic pressure and diameter were not significantly different from control. LV dP/dt was elevated by 7.1 +/- 1.1%, heart rate was elevated by 25 +/- 3.3 beats/min, and cardiac output remained elevated by 54 +/- 7.4%. At this time, coronary cross-sectional area was elevated by 26 +/- 3.0%, late diastolic coronary vascular resistance was reduced by 50 +/- 2.7%, and total peripheral resistance was 40 +/- 3.8% below control. The coronary sinus oxygen content was elevated by 3.4 +/- 0.8 vol% and the arteriovenous oxygen difference fell by 3.5 +/- 0.8 vol%. After beta-adrenergic blockade with propranolol and with heart rate constant or varying, the increases in coronary cross-sectional area and decreases in late diastolic coronary vascular resistance induced by nifedipine were still observed, but were significantly smaller (p less than 0.01). Thus, nifedipine dilates both large coronary arteries and coronary resistance vessels, effects that could be attributed in part to beta-adrenergic mechanisms. Nifedipine also exerts potent effects on coronary and peripheral arterial vessels, but has little effect on preload.
Pathophysiology of coronary artery spasm.
Authors: Freedman B , Richmond D R , Kelly D T
Published: June 2011

Coronary arterial measurements were made from cineangiograms in patients with positive and negative ergonovine tests. In those with positive tests, normal segments of arteries adjacent to the site of spasm and arteries without spasm showed no greater sensitivity to ergonovine than arteries from control patients (20 +/- 13% constriction vs 17 +/- 12%, NS). In patients with positive and negative ergonovine tests, constriction was measured at lesion sites after ergonovine and compared with values predicted from a geometric theory. The measured constriction was always greater than predicted in patients with a positive ergonovine test, and frequently less than predicted in patients with a negative test. The increased sensitivity of arteries that show localized vasospasm at lesion sites after ergonovine administration is not explained by geometry alone.
Assessment of transesophageal pulsed Doppler echocardiography in the detection of mitral regurgitation.
Authors: Schlüter M , Langenstein B A , Hanrath P , Kremer P , Bleifeld W
Published: June 2011

The value of transesophageal pulsed Doppler echocardiography (PDE) was studied in six patients with competent mitral valve and in 12 patients with angiographically proved mild to moderately severe mitral regurgitation. The results were compared with those from the standard transthoracic method of investigation. The advantages of the esophageal over the transthoracic approach in the detection of mitral regurgitation are (1) absence of anatomic obstacles between the ultrasound transducer and the heart; (2) nearly parallel alignment of the ultrasound beam with the blood flow direction; (3) the use of high pulse repetition frequencies; and (4) detection of localized regurgitant jets by left atrial scanning. This results in a superior recording quality and greater sensitivity. Based on a specific systolic flow pattern in the time-interval histogram, mitral regurgitation was detected in all patients by the transesophageal technique (100% sensitivity), but in only 58% by the precordial approach. Thus, transesophageal pulsed Doppler echocardiography can accurately detect the presence of mitral regurgitation, particularly in cases of mild or moderate severity.
Comparison of thallium-201 scanning in idiopathic dilated cardiomyopathy and severe coronary artery disease.
Authors: Dunn R F , Uren R F , Sadick N , Bautovich G , McLaughlin A , Hiroe M , Kelly D T
Published: June 2011

To determine whether cardiomyopathy could be distinguished from coronary artery disease, we used thallium scanning to study 25 patients with severe left ventricular dysfunction and chronic heart failure. Ten patients had normal coronary arteries and idiopathic cardiomyopathy (ejection fraction 20 +/- 5%), and 15 patients had multivessel coronary disease and left ventricular dysfunction (ejection fraction 25 +/- 6%). The exercise time and maximal heart rate were similar in the two groups. Two patients with cardiomyopathy and 11 with coronary artery disease had a positive exercise ECG (p less than 0.05). Thallium scans showed perfusion defects in all 25 patients. The perfusion defects were complete in nine coronary artery disease patients (60%) and in one patient (10%) with cardiomyopathy (p less than 0.05). Extensive defects involving more than 40% of the left ventricular circumference, the number of segments involved, redistribution on the 4-hour scan, lung uptake and ventricular size were similar in the two groups. Perfusion defects on thallium scanning can occur in patients with idiopathic dilated cardiomyopathy and chronic heart failure. Thallium scanning cannot be reliably used in patients with chronic heart failure to distinguish coronary artery disease from cardiomyopathy unless complete defects are present.
Quantification of experimental myocardial infarction using nuclear magnetic resonance imaging and paramagnetic ion contrast enhancement in excised canine hearts.
Authors: Goldman M R , Brady T J , Pykett I L , Burt C T , Buonanno F S , Kistler J P , Newhouse J H , Hinshaw W S , Pohost G M
Published: June 2011

Determination of myocardial infarct size is important for clinical management of patients with ischemic heart disease and for research on limiting infarct size. Nuclear magnetic resonance (NMR) imaging permits tomographic depiction of the distribution of mobile tissue protons. NMR images have demonstrated high spatial resolution and contrast. To evaluate the potential of this technique in measuring myocardial infarct size, NMR imaging was performed in six canine hearts excised 24 hours after circumflex coronary artery ligation. Before sacrifice, the dogs received i.v. manganous chloride (0.05 mmol/kg). After NMR imaging, the heart were sectioned and the myocardial slices were stained with triphenyl tetrazolium chloride. The pathologically determined infarct size was compared with the infarct size measured by NMR imaging. The correlation was good (regression line slope 1.06; r = 0.94). We conclude that NMR imaging with paramagnetic contrast agents can be used to determine infarct size in excised hearts.
Accuracy of serial myocardial perfusion scintigraphy with thallium-201 for prediction of graft patency early and late after coronary artery bypass surgery. A controlled prospective study.
Authors: Pfisterer M , Emmenegger H , Schmitt H E , Müller-Brand J , Hasse J , Grädel E , Laver M B , Burckhardt D , Burkart F
Published: June 2011

To assess the accuracy of serial myocardial perfusion scintigraphy with thallium-201 (201Tl) to predict graft patency early and late coronary artery bypass surgery, rest and exercise 201Tl and coronary arteriography were performed preoperatively and 2 weeks and 1 year after operation. The scintigraphic results were compared with graft patency, symptoms, left ventricular function and physical work capacity in a consecutive series of 55 patients with a total of 154 grafts. Serial 201Tl had an 80% sensitivity, 88% specificity and 86% overall accuracy in detecting or excluding graft occlusion, which was predicted by reversible ischemia as well as persistent "new scar" segments. Occluded grafts were correctly localized by 201Tl scintigraphy in 61%. Postoperative apical 201Tl defects were frequent (two-thirds of cases), and were the result of intraoperative transapical venting of the left ventricle. After coronary bypass graft surgery, ejection fraction at rest was unchanged. Left ventricular end-diastolic pressure and physical work capacity improved significantly. In the presence of new perfusion defects detected postoperatively, physical work capacity was reduced significantly. New 201Tl defects in addition to typical or atypical angina provided a high probability of graft occlusion, while in the absence of new 201Tl defects all grafts were patent in more than 90% of patients, all of whom had no or only atypical chest pain. We conclude that serial 201Tl imaging after coronary artery bypass surgery is an accurate noninvasive method that can be used routinely to assess graft function, to localize spatially occluded grafts and to identify patients with a high likelihood of graft occlusion who may need invasive studies.
Epicardial mapping of segmental myocardial function: an echocardiographic method applicable in man.
Authors: Likoff M , Reichek N , St John Sutton M , Macoviak J , Harken A
Published: June 2011

A technique for epicardial mapping of segmental myocardial function at multiple sites over both right and left ventricles was developed using a high-resolution, 7.5-MHz, short-focus, miniaturized, M-mode echocardiographic transducer worn on the fingertip. Myocardial function was determined from the extent and time course of systolic thickening and diastolic thinning at each site mapped. The technique was characterized in an open-chest canine model of myocardial ischemia. Ischemia was induced by transient or permanent coronary occlusion in 17 dogs. Acute occlusions produced reduced segmental thickening within 10-15 seconds and, often, overt systolic thinning of ischemic myocardium. Rhodamine fluorescence perfusion maps were compared with echocardiographic maps in nine dogs. Segmental thickening was reduced in perfused segments adjacent to, but not involved by, ischemia, as well as ischemic segments. Reproducibility appeared satisfactory for quantitative analysis of grouped data on multiple segments, and qualitative analysis in individual segments. Initial human studies performed during coronary bypass surgery in 11 subjects showed echocardiographic abnormalities in the six patients with ventriculographic abnormalities and in four with normal ventriculograms. Transmural infarctions were akinetic, showing no change in thickness throughout the cardiac cycle. Hypokinetic segments distal to high-grade coronary stenosis were common, although most segments distal to stenosis contracted normally. Reversal of segmental contraction abnormalities by coronary bypass grafting was shown in three subjects, while worsening of function was seen in previously abnormal segments in two and in a previously normal segment in one subject. Epicardial echocardiographic mapping is a practical method for intraoperative assessment of myocardial function during coronary surgery in man that may enhance our understanding of the pathophysiology of coronary disease and the effects of coronary surgery.
Myocardial function in areas of heterogeneous perfusion after coronary artery occlusion in conscious dogs.
Authors: Cox D A , Vatner S F
Published: June 2011

Regional myocardial function and blood flow in endocardial layers were correlated in myocardial segments subtending severely ischemic and adjacent, normally perfused myocardium in conscious dogs 1--3 weeks after recovery from coronary artery occlusion. With coronary artery occlusion induced by a hydraulic occluder, endocardial blood flow (measured with radioactive microspheres) and function (determined with an ultrasonic dimension gauge) in homogeneously nonischemic segments increased slightly but not significantly. In homogeneously ischemic segments, blood flow and function decreased (p less than 0.01) by 96 +/- 1% and 98 +/- 4%, respectively. In segments subtending zones of unequal perfusion, endocardial blood flow increased nonsignificantly in the myocardium surrounding the nonischemic crystal, while decreasing by 93 +/- 2% (p less than 0.01) in myocardium surrounding the ischemic crystal. Surprisingly, these segments behaved like homogeneously ischemic segments, i.e., endocardial shortening decreased by 92 +/- 6% (p less than 0.01). Thus, the failure to detect shortening despite normal perfusion of the myocardium surrounding one of the transducers suggest a potential problem with interpretation of regional function measurements or an inability of the apparently nonischemic myocardium to contract.
Improved left ventricular diastolic filling in patients with coronary artery disease after percutaneous transluminal coronary angioplasty.
Authors: Bonow R O , Kent K M , Rosing D R , Lipson L C , Bacharach S L , Green M V , Epstein S E
Published: June 2011

Left ventricular (LV) diastolic filling is abnormal at rest in many patients with coronary artery disease (CAD), even in the presence of normal resting LV systolic function. To determine the effects of improved myocardial perfusion on impaired. LV diastolic filling, we studied 25 patients with one-vessel CAD by high-temporal-resolution radionuclide angiography before and after percutaneous transluminal coronary angioplasty (PTCA). No patient had ECG evidence of previous myocardial infarction. Despite normal regional and global LV systolic function at rest in all patents, LV diastolic filling was abnormal (peak LV filling rate [PFR] less than 2.5 end-diastolic volumes (EDV)/sec or time to PFR greater than 180 msec) in 17 of 25 patients. Twenty-three patients had abnormal LV systolic function during exercise. After successful PTCA, LV ejection fraction and heart rate at rest were unchanged, but LV ejection fraction during exercise increased, from 52 +/- 8% (+/- SD) to 63 +/- 5% (p less than 0.001). LV diastolic filling at rest improved: PFR increased from 2.3 +/- 0.6 to 2.8 +/- 0.5 EDV/sec (p less than 0.001) and time to PFR decreased from 181 +/- 22 to 160 +/- 18 msec (p less than 0.001). Thus, a reduction in exercise-induced LV systolic dysfunction after PTCA, reflecting a reduction in reversible ischemia, was associated with improved LV diastolic filling at rest. These data suggest that in many CAD patients with normal resting LV systolic function and without previous infarction, abnormalities of resting LV diastolic filling are not fixed, but appear to be reversible manifestations of impaired coronary flow.
High-density lipoprotein cholesterol and prognosis after myocardial infarction.
Authors: Berge K G , Canner P L , Hainline A
Published: June 2011

The Coronary Drug Project was a randomized, placebo-controlled trial of lipid-influencing drugs in men who had recovered from one or more documented myocardial infarctions. Determinations of high-density lipoprotein (HDL) cholesterol were made at baseline in a group of 354 men randomized to the placebo group. Five-year mortality was highest (33.0%) in men with baseline serum HDL cholesterol levels of less than 35 mg/dl; it was 15.9%, 17.7%, and 21.8% in men with levels of 35--39, 40--44, and greater than or equal to 45 mg/dl, respectively (for the linear inverse relationship between HDL cholesterol and 5-year mortality, p = 0.029). Adjustment for 40 baseline variables had a minimal effect on this relationship (p = 0.042).
Timolol-related reduction in mortality and reinfarction in patients ages 65-75 years surviving acute myocardial infarction. Prepared for the Norwegian Multicentre Study Group.
Authors: Gundersen T , Abrahamsen A M , Kjekshus J , Rønnevik P K
Published: June 2011

Long-term treatment with timolol in patients ages 65--75 years who survived myocardial infarction was related to a significant reduction, compared with placebo, in overall mortality (p less than 0.05), total cardiac death (p less than 0.01), sudden death (p less than 0.05) and reinfarction (p less than 0.01). The analyses were based on 732 patients (384 taking placebo and 348 timolol) from a cohort of 1884 patients in the Norwegian multicenter timolol study. The dosage of timolol was 10 mg twice daily and the patients were followed for 12--33 months (mean 17 months). There were 83 deaths in the placebo group and 52 deaths in the timolol group, a reduction of 35.5%. There were 69 initial reinfarctions in the placebo group and 38 in the timolol group, a reduction of 39.2%. There was no difference in the reduction of mortality and reinfarction between patients 65--75 years of age and patients less than 65 years of age. The incidence of side effects, the number of withdrawals and the reasons for withdrawal were similar in older and younger patients. We conclude that age should not be a decision-making factor concerning timolol therapy in postinfarct patients.
Electrotonic metabolism of pacemaker activity. Further biological and mathematical observations on the behavior of modulated parasystole.
Authors: Antzelevitch C , Jalife J , Moe G K
Published: June 2011

An in vitro biologic model of parasystole and a mathematical model of parasystole based on the phase-response relationships derived from the biologic model were used in tandem to further develop our understanding of the patterns of ectopic activity that might arise as a consequence of the interaction of two pacemakers across a zone of block. Superfusion of the central segment of a dog Purkinje fiber with an ion-free isotonic sucrose solution provided a narrow region of block. The modulation of pacemaker activity by electronic potentials transmitted across the area of block was shown to be importantly influenced by the position of the "ectopic" pacemaker relative to the site of block. Effects of repetitive electrotonic influences on a single pacemaker cycle, the degree of entrance block and capture of the pacemaker during a phase of supernormal excitability were also studied in both the biologic and mathematical models. Our results indicate that marked shifts in the incidence and pattern of manifest ectopic activity can occur as a result of slight changes in heart rate, ectopic pacemaker rate, level of block and the position of the parasystolic pacemaker relative to the block border.
Thallium-201 uptake in variant angina: probable demonstration of myocardial reactive hyperemia in man.
Authors: Kronenberg M W , Robertson R M , Born M L , Steckley R A , Robertson D , Friesinger G C
Published: June 2011

Myocardial thallium scintigraphy was performed in four subjects with variant angina and in one subject with isolated, fixed coronary obstruction. Three subjects with variant angina had short episodes of ischemic ST-segment elevation that lasted 20--100 seconds. Thallium scintigrams demonstrated excess uptake in regions judged to be ischemic by angiographic and electrocardiographic criteria. Two subjects, one with variant angina and the other with a fixed coronary lesion, had prolonged episodes of ischemia that lasted 390--900 seconds. Both had reduced thallium uptake in the ischemic regions. We conclude that myocardial reactive hyperemia is the cause of excess thallium uptake in patients with variant angina who have short episodes of myocardial ischemia.
Contribution of variable entrance and exit block in protected foci to arrhythmogenesis in isolated ventricular tissues.
Authors: Rosenthal J E , Ferrier G R
Published: June 2011

Automatic foci with membrane potentials in the range characterized by depolarization-induced automaticity exhibit entrance block. The present study demonstrates a role of variable entrance and exit block in arrhythmogenesis. We studied canine interventricular septa with the right bundle branch exposed, isolated false tendons and isolated feline papillary muscle using standard microelectrode techniques. Foci of automaticity were produced either by focal application of electric current or by exposure of the preparations to Tyrode's solution containing 1.5-2.0 mM KCl. Foci induced by mild depolarization exhibited entrance block with exit conduction and were subject to electrotonic modulation. With greater depolarization, varying degrees of exit block developed. Various rhythms, including Wenckebach periodicity, resulted. Delayed emergence of electrotonically accelerated activity led to closely coupled extrasystoles resembling reentrant activity. Exit conduction in some preparations was facilitated by enhanced normal pacemaker activity (membrane potentials -- 70 mV or greater) in tissue peripheral to the focus. Also, when there were two sites of automaticity separated by an area of depressed conduction, intermodulation between the two automatic regions generated complex arrhythmias. Shifts in maximum diastolic potential also changed conduction and led to changes in arrhythmic patterns. In some experiments, focal automaticity was terminated by single stimuli. We conclude that complex and variable behavior of automatic foci may result in activity with characteristics previously attributed to other arrhythmic mechanisms.
Reentrant ventricular arrhythmias in the late myocardial infarction period. 9. Electrophysiologic-anatomic correlation of reentrant circuits.
Authors: Mehra R , Zeiler R H , Gough W B , El-Sherif N
Published: June 2011

We studied isochronal maps of ventricular activation during ventricular arrhythmias induced by programmed premature stimulation in dogs 3-5 days after ligation of the left anterior descending coronary artery. The entire epicardial surface and selective intramural sites were recorded using a computerized multiplexing technique. The electrophysiologic data were correlated with the anatomic characteristics of the infarction. In nine of 17 dogs (55%), the induced ventricular rhythm was due to reentrant activation in the surviving epicardial layer overlying the infarction. The irregular epicardial layer (up to 4 mm thick) had grossly intact myocardial fibers on microscopic examination but showed abnormal electrophysiologic characteristics. The stimulated premature beat that initiated reentry produced a continuous arc of functional conduction block within the surviving epicardial layer. The activation wave front circulated slowly around both ends of the arc of block, rejoined on the distal side of the arc before breaking through the arc to reactivate an area proximal to the block. This resulted in splitting of the initial single arc of block into two arcs. Reentrant activation continued as two synchronous circuits that traveled clockwise around one arc and counterwise around the other. Reentry spontaneously terminated when the leading edge of both reentrant circuits encountered refractory tissue, resulting in the coalescence of the two arcs of block into one. The present study may increase the understanding of the electrophysiologic mechanism of some ventricular repetitive responses and tachyarrhythmias induced by programmed premature stimulation in the clinical laboratory.
Nucleotide degradation and functional impairment during cardioplegia: amelioration by inosine.
Authors: DeWitt D F , Jochim K E , Behrendt D M
Published: June 2011

The degradation of adenine nucleotide levels and impairment of functional recovery associated with exposure to hypothermic (20 degrees C) cardioplegia was studied in 84 isolated working rat hearts. After a 1-hour control period, hearts were exposed to 1 hour of cardioplegia that consisted of increasingly longer periods of cardioplegic solution (CPS) infusion (30 seconds and 10, 30 and 60 minutes), followed by increasingly shorter periods of global ischemia (591/2 minutes and 50, 30 and 0 minutes). Hearts were then reperfused for 1 hour with control perfusate, during which recovery of cardiac output was monitored. Additional hearts were freeze-clamped at various points in the protocols to determine adenine nucleotide levels (ATP, ADP, AMP and their sum TAN). Exposure to increasingly longer periods of CPS perfusion resulted in proportionally greater degradation of nucleotides and poorer recovery of cardiac output. Addition of inosine to the recovery perfusate as well as the CPS further improved nucleotide levels and recovery of cardiac output. These results suggest that washout of nucleotide degradation products in the CPS or reperfusion prevents their salvage for nucleotide resynthesis and impairs functional recovery from cardioplegia.
Extensive myocardial fiber disarray in aortic and pulmonary atresia. Relevance to hypertrophic cardiomyopathy.
Authors: Bulkley B H , D'Amico B , Taylor A L
Published: June 2011

Myocardial fiber disarray is a distinctive histopathologic finding seen in asymmetric hypertrophic cardiomyopathy. We studied 14 hearts with aortic atresia and intact interventricular septum, six hearts with pulmonic atresia and intact interventricular septum, eight normal infant hearts matched for age of the study hearts, and one nonadult heart with hypertrophic cardiomyopathy and asymmetric hypertrophy and quantitatively analyzed tissue sections through both ventricles and the septum. Normal hearts had an average overall fiber disarray of 8.7% (range 3.8-17%) of the left ventricle including septum. Hearts with pulmonary atresia had an overall disarray of 70.4% (range 13-97%) of the entire right ventricle, and those with aortic atresia 62.1% (range 26-97%) of the left ventricle. The one infant heart with hypertrophic cardiomyopathy showed 15.5% disorder of the left ventricular free wall, 75% disorder of the septum and 47% overall myocardial fiber disarray. Thus, while quantitative criterion distinguished normal from abnormal hearts, they did not distinguish among the various pathologic states. Although extensive myocardial fiber disarray is not exclusive to, or pathognomonic of, hypertrophic cardiomyopathy, it is a useful finding taken in the context of the overall disease. The sensitivity and specificity of this isolated morphologic observation as an indication of hypertrophic cardiomyopathy may be misleading.
A mechanism of torsades de pointes in a canine model.
Authors: Bardy G H , Ungerleider R M , Smith W M , Ideker R E
Published: June 2011

A dog model of torsades de pointes (TdP) was developed. Twenty 18-30-kg dogs had cardiopulmonary bypass instituted to maintain stable temperature, perfusion pressure and oxygenation. Quinidine, 30 mg/kg, was then administered and burst ventricular pacing was used to induce arrhythmias. The left anterior descending coronary artery was occluded for 15 minutes and repeat pacing studies were performed. Maps of epicardial activation were made from 27 simultaneously recorded electrograms obtained from 1-mm bipolar electrodes secured to the epicardium with a nylon mesh sock. Arrhythmias in five dogs met criteria for the diagnosis of TdP: All had the characteristic undulating QRS morphology typically associated with TdP, all occurred in the setting of QT prolongation and all ended spontaneously. The epicardial maps demonstrated that each change in QRS morphology was associated with a change in the site of epicardial breakthrough. Those QRS complexes during the transition from one morphology to the next were associated with fusion cycles in which both the old and new sites of epicardial breakthrough were present. In essence, two or more competing activation sequences were vying for control of epicardial depolarization. This conclusion was strengthened by our ability to simulate TdP in the surface ECG and in epicardial maps by simultaneously pacing from two widely separated ventricular sites at slightly different, varying rates.
Use of alternating current during diagnostic electrophysiologic studies.
Authors: Mower M M , Reid P R , Watkins L , Mirowski M
Published: June 2011

When conventional programmed electrical stimulation did not yield ventricular arrhythmias suitable for testing implanted automatic defibrillator function and for mapping the location of arrhythmogenic foci, full-wave rectified alternating current (120 Hz) was used for inducing arrhythmias. Application of alternating current resulted in ventricular tachycardias 31 times; in 27 instances, these tachycardias were similar in rate (216 +/- 37 beats/min) and morphology to those previously induced in the same patient by programmed electrical stimulation (191 +/- 30 beats/min). During endocardial mapping, the origin of the tachycardias induced by both methods was found in the same region. Alternating current produced ventricular fibrillation only four times, twice when it was the patient's spontaneous native arrhythmia and twice after apparently effective endocardial resection. No complications of the technique were observed. The use of alternating current was found to be simple, rapid and safe; it may be especially useful in the operating room during antiarrhythmic surgery because it markedly reduces the cardiopulmonary bypass time required for induction and may also be useful for testing the adequacy of endocardial resection.
Sudden sinus slowing with junctional escape: a common mode of initiation of juvenile supraventricular tachycardia.
Authors: Levy A M , Bonazinga B J
Published: June 2011

After noting bradycardia-induced supraventricular tachycardia (SVT) in two successive children with SVT, we analyzed Holter monitor recordings done on 66 children with suspected or proved SVT. Ten children had apparent reentry SVT. The most common mode of initiation (eight of 10 patients) was not premature atrial beats, but sudden sinus pause with a junctional escape beat (JEB), usually fused with the delayed sinus P wave, initiating the tachycardia. Electrophysiologic studies in five children who had this mode of initiation showed evidence of reentry in four, possibly by dual atrioventricular nodal (AVN) pathways. Since sudden sinus pause and JEB are relatively uncommon in adults, the disappearance of this phenomenon with age may be the most significant reason why children often have less tachyarrhythmia as they get older. Both propranolol and digoxin significantly increased the numbers of episodes of SVT in the three patients tested with serial Holter monitoring.
Origin of the third heart sound. II. Studies in human subjects.
Authors: Ozawa Y , Smith D , Craige E
Published: June 2011

We report noninvasive and invasive studies designed to clarify the mechanism of the third heart sound (S3) in humans. The noninvasive observations were made using a miniature accelerometer attached to the skin surface at the cardiac apex. In subjects with no S3, the tracings were either flat or showed very low undulations throughout diastole. Those with an S3, however, demonstrated a distinct reduction of acceleration, or negative jerk, of the rapid filling movement at the apex at the time of the sound. The invasive studies in the cardiac catheterization laboratory consisted of frame-by-frame measurements of left ventricular dimensions in the transverse and long axes during early diastole in patients with diastolic overload abnormalities to investigate the temporal sequence of filling in these two principal axes. The maximal long-axis filling rate occurred after the short axis, a finding that helps to resolve a discrepancy noted in the time of maximal short-axis filling and S3 production. These studies support the concept that the S3 is due to a sudden intrinsic limitation of longitudinal expansion of the left ventricular wall during early diastolic filling, resulting in a negative jerk that is transmitted to the skin surface.
Physical fitness and blood pressure in school children.
Authors: Fraser G E , Phillips R L , Harris R
Published: June 2011

We studied the relationship between physical fitness and blood pressure in 228 school children. The data were collected as part of the Loma Linda Child-Adolescent Blood Pressure Study. Systolic and diastolic blood pressures were lower in children above average fitness than in children below average fitness among preadolescent and adolescent boys and girls. On multivariate analysis, adjusting for skinfold thickness, an index of lean arm mass, height and age, the relationship between fitness and systolic blood pressure was statistically significant for preadolescent boys and for adolescents of both sexes. The multivariate relationship was not clearly seen for diastolic blood pressure. Multivariate techniques showed that significant correlates of fitness were obesity in preadolescents, age in adolescent boys and height in adolescent girls. Predicted pulse rates for stages 6-10 of a modified Balke treadmill protocol are given in appendix 1 for preadolescent and adolescent boys and girls.
Effects of oral verapamil in patients with atrioventricular reentrant tachycardia incorporating an accessory pathway.
Authors: Wu D , Kou H C , Yeh S J , Lin F C , Hung J S
Published: June 2011

In 14 patients with atrioventricular reentrant tachycardia incorporating an accessory pathway, electrophysiologic studies were performed before and serially at 0.5--1-hour intervals for 6 hours after the fourth dose of 80 mg of oral verapamil given every 6 hours. Verapamil increased both the longest atrial paced cycle length producing type 1 atrioventricular block and the effective refractory period of the atrioventricular conduction system at all measurements. Before verapamil, sustained tachycardia could be induced in all 14 patients. After verapamil, six patients had induction of echo beats alone at all measurements, and in eight patients nonsustained or sustained tachycardia could be induced, particularly after the fourth hour. Follow-up study with oral verapamil at the same dosage in 13 patients for 7 +/- 5 months (+/- SD) revealed that the six patients with induction of echo beats alone have been free of symptomatic arrhythmia, while six of the remaining eight patients had occasional attacks of sustained tachycardia. Thus, oral verapamil increases atrioventricular nodal refractoriness, with an effect lasting up to 6 hours. Electrophysiologic study performed 5-6 hours after verapamil can be used to predict clinical responses in patients with atrioventricular reentrant tachycardia.