bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction.
Authors: Van de Werf F , Vanhaecke J , de Geest H , Verstraete M , Collen D
Published: June 2011

Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 micrograms/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the alpha 2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20 micrograms/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 +/- 17 min (mean +/- SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4 micrograms/ml (range 4.0 to 13.3). At the end of the infusion the alpha 2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 micrograms/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Frequency-dependent effects of calcium antagonists on atrioventricular conduction and refractoriness: demonstration and characterization in anesthetized dogs.
Authors: Talajic M , Nattel S
Published: June 2011

Calcium-channel blockers are known to affect slow inward current in a frequency-dependent fashion. The purpose of these experiments was to study use-dependent effects of verapamil, diltiazem, and nifedipine on atrioventricular conduction in vivo. Loading and maintenance infusion techniques were developed to study each drug at a series of stable plasma concentrations in autonomically blocked dogs anesthetized with morphine and alpha-chloralose. All three agents produced changes in atrioventricular conduction and refractoriness that increased with increasing stimulation frequency. The time dependence of drug-induced changes in atrioventricular conduction was characterized both by varying the coupling of single test stimuli and by abruptly changing activation frequency. The time constants for onset of (tau on) and recovery from (tau off) block were typical for each drug, with nifedipine having a faster time constant (tau off = 0.36 +/- 0.12 sec) than verapamil (tau off = 3.2 +/- 1.0 sec, tau on = 28 +/- 8 sec) or diltiazem (tau off = 2.7 +/- 1.2 sec, tau on = 13 +/- 4 sec). The time constants for each drug were independent of concentration but the magnitude of time-dependent change increased with increasing drug concentration. We conclude that calcium-channel blockers have important frequency-dependent effects on atrioventricular conduction in vivo. This frequency dependence may result in selective depression of atrioventricular conduction in the presence of supraventricular tachyarrhythmias, with important potential implications for the clinical use of these agents.
Characteristics of initiation and termination of catecholamine-induced triggered activity in atrial fibers of the coronary sinus.
Authors: Johnson N , Danilo P , Wit A L , Rosen M R
Published: June 2011

We studied epinephrine-induced delayed afterdepolarizations and triggered activity in atrial fibers from the canine coronary sinus to determine whether their responses to cardiac pacing would aid in formulating a uniform set of guidelines for differentiating this triggered activity from other arrhythmogenic mechanisms. We used standard microelectrode techniques and compared the delayed afterdepolarizations and triggered activity with those occurring in ouabain-superfused Purkinje fibers. Like Purkinje fibers, the frequency of triggering in the coronary sinus and the coupling interval of the first triggered beat were related directly to the basic drive cycle length, and the delayed afterdepolarization amplitude and frequency of triggering were related to the coupling interval of premature stimuli (S2). However, unlike Purkinje fibers, the coupling interval of the delayed afterdepolarization and of the first triggered beat were independent of the S2. Once initiated, triggered activity in the coronary sinus followed one of four rhythm patterns: in all four, the minimum and equilibrium cycle lengths were independent of the initiating cycle length. Triggered activity was terminated by overdrive and S2 pacing, especially by long episodes of overdrive at short cycle length. The first escape beat after overdrive was linearly related to the overdrive cycle length, resulting in overdrive acceleration. The return cycle length after S2 was linearly related to the S2 coupling interval. Because delayed afterdepolarizations and triggered activity in the coronary sinus respond differently to pacing from those in ouabain-superfused Purkinje fibers, triggered activity in general may not be identified by a uniform set of guidelines.
Inhibition of platelet aggregability by moderate-intensity physical exercise: a randomized clinical trial in overweight men.
Authors: Rauramaa R , Salonen J T , Seppänen K , Salonen R , Venäläinen J M , Ihanainen M , Rissanen V
Published: June 2011

It has been postulated that platelet function plays an important role in the initiation of atherosclerosis. Currently there are no definitive data on the longer-term effects of regular physical exercise on platelet function in humans. We assessed the influence of regular moderate-intensity physical exercise (brisk walking to slow jogging) on platelet aggregation in a population-based sample of middle-aged, overweight, mildly hypertensive men in eastern Finland. In this controlled study, we evaluated the net effect of exercise on platelet aggregation by studying changes in optical density and ATP release in platelet-rich plasma. A significant inhibition of secondary platelet aggregation from 27% to 36% was observed in the men taking regular exercise. These findings give new insight into the possible protective effects of exercise against the risk of ischemic heart disease.
High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: the Lipid Research Clinics Coronary Primary Prevention Trial.
Authors: Gordon D J , Knoke J , Probstfield J L , Superko R , Tyroler H A
Published: June 2011

Plasma levels of high-density lipoprotein cholesterol (HDL-C) at entry and subsequent changes from these baseline levels were inversely predictive of coronary heart disease (CHD) end points in hypercholesterolemic men followed for 7 to 10 years in the Lipid Research Clinics Coronary Primary Prevention Trial, especially in the 1907 participants receiving cholestyramine. When the men in this cohort were compared, each 1 mg/dl increment in baseline HDL-C (mean 44.3 mg/dl) was associated with a 5.5% decrement in risk of "definite" CHD death or myocardial infarction (Z = -5.4), and each 1 mg/dl increase from baseline HDL-C levels (mean increase = 1.6 mg/dl) during the trial was associated with a 4.4% risk reduction (Z = -2.2). In the 1899 participants receiving placebo, the corresponding risk decrements were 3.4% and 1.1%. Although baseline HDL-C level (mean = 44.4 mg/dl) remained a significant risk predictor (Z = -3.8) in the placebo cohort, increases in HDL-C (mean increase 0.5 mg/dl) were not significantly predictive of CHD (Z = -0.6) unless "suspect" as well as "definite" end points were analyzed (Z = -2.0). When the associations between HDL-C (baseline plus change) and incidence of definite CHD end points within each treatment cohort were compared, their difference approached nominal significance (Z = 1.9). The results suggest a synergistic interaction, in which cholestyramine treatment reduced CHD risk most substantially in men maintaining the highest HDL-C levels.
Local coronary supersensitivity to diverse vasoconstrictive stimuli in patients with variant angina.
Authors: Kaski J C , Crea F , Meran D , Rodriguez L , Araujo L , Chierchia S , Davies G , Maseri A
Published: June 2011

It has been shown in different groups of patients with variant angina that coronary spasm can be reproduced by physiologic maneuvers and pharmacologic agents. It is not known, however, to what extent different stimuli can induce spasm in the same patient. To investigate whether coronary arterial spasm results from specific abnormal agonist-receptor interactions or from a local nonspecific coronary supersensitivity to different stimuli, 28 patients with vasospastic angina were submitted to a series of diverse vasoconstrictive stimuli known to provoke coronary spasm. Ergonovine, hyperventilation, handgrip, cold pressor, and exercise-tests, were carried out in all 28 patients. In the last 15 patients histamine was also administered. Spasm was provoked by ergonovine in 96% of patients, by hyperventilation in 54%, by histamine in 47%, by exercise in 46%, and by the cold pressor and handgrip tests in 11% and 7%, respectively. No significant differences were found in the responses to provocative tests of patients with normal coronary arteries or nonsignificant stenoses and those with significant lesions. In the same individual, spasm was induced by at least two vasoconstrictive stimuli, although with a different mechanism of action, in 82% of patients and spasm was induced by three or more stimuli in 39%. Tests were repeated in at least 23 patients and short-term reproducibility paralleled sensitivity. These results suggest that in patients with variant angina, a local nonspecific supersensitivity rather than an abnormal specific agonist-receptor interaction plays a major role in the genesis of coronary arterial spasm.
Quantitative analysis of myocardial infarct structure in patients with ventricular tachycardia.
Authors: Bolick D R , Hackel D B , Reimer K A , Ideker R E
Published: June 2011

To study whether myocardial infarction differs in patients with and without ventricular tachycardia, the hearts of 22 deceased patients with ventricular tachycardia and 21 deceased control patients were analyzed quantitatively. The hearts from the ventricular tachycardia group were heavier and more dilated than those from the control group. Histologic analysis of a representative cross section from each heart showed that the ventricular tachycardia group had larger, more solid infarcts than did the control group. The ventricular tachycardia group also had a greater area of spared subendocardium, more hydropic change of the spared subendocardium, and more "ribbon type" spared subendocardium, which was defined as spared subendocardium of uniform contour 1 mm thick or less. The ventricular tachycardia group was divided into a subacute subgroup (n = 14, dying less than or equal to 10 weeks after infarction) and a chronic subgroup (n = 8, dying greater than 10 weeks after infarction). The infarcts of the subacute ventricular tachycardia group were more solid and had a greater amount of ribbon type spared subendocardium than those of the chronic ventricular tachycardia group. This information can serve as a baseline for the evaluation of animal preparations of tachycardia and, when combined with knowledge of the location of the arrhythmogenic region furnished by intraoperative mapping, should lead to better understanding of the anatomic substrate for ventricular tachycardia.
Late potentials detected after myocardial infarction: natural history and prognostic significance.
Authors: Kuchar D L , Thorburn C W , Sammel N L
Published: June 2011

The risk of developing spontaneous ventricular tachycardia (VT) and/or sudden death ("arrhythmic events") was prospectively assessed in 165 patients who survived acute myocardial infarction. Signal-averaged electrocardiograms (ECGs) were performed before hospital discharge and then serially at regular intervals over the following year. In addition, 24 hr Holter monitoring was performed and left ventricular ejection fraction was determined. Sixty-five patients (group 1) had abnormal signal-averaged ECGs (voltage in the last 40 msec of the filtered QRS less than 20 microV or filtered QRS duration greater than 120 msec), 92 had normal signal-averaged ECGs (group 2), and eight had bundle branch block (excluded from analysis). In group 1, spontaneous normalization of the voltage in the last 40 msec of the QRS complex occurred in 30% of patients after 12 months, although total filtered QRS duration did not change overall. During follow-up of up to 20 months (median 11), seven patients died suddenly and six presented again with spontaneous, symptomatic VT. Eleven of 65 (17%) group 1 patients had an arrhythmic event compared with one of 92 patients (1%) in group 2 (p less than .001). The sensitivity of the signal-averaged ECG as a predictor of arrhythmic events was 92% with a specificity of 62%. Patients with subsequent arrhythmic events had considerably lower voltage in the last 40 msec of the QRS (11.0 +/- 8.3 vs 32.0 +/- 21.9 microV; p less than .001) than those without such events, and longer filtered QRS complexes (121 +/- 14 vs 105 +/- 12 msec; p less than .001). Multivariate logistic regression determined that the signal-averaged ECG provided independent prognostic information from the presence of complex ventricular ectopy and the degree of left ventricular dysfunction assessed at the time of hospital discharge. Signal-averaged ECGs provide important prognostic information in identifying patients at risk of arrhythmic events after myocardial infarction. Dynamic changes in the terminal QRS voltage are observed during the first year after myocardial infarction.
Characterization of the spatial distribution of late ventricular potentials by body surface mapping in patients with ventricular tachycardia.
Authors: Faugère G , Savard P , Nadeau R A , Derome D , Shenasa M , Page P L , Guardo R
Published: June 2011

Low-level activity at the end of the QRS complex was analyzed from 63 thoracic leads in 15 normal subjects and in 21 patients with ventricular tachycardia (VT). The latter had old myocardial infarction and no conduction disturbances and had not been receiving antiarrhythmic drugs. In both normal subjects and patients with VT, isopotential maps of the time-averaged and filtered (25 Hz high-pass) electrocardiograms during the terminal portion of the QRS were dipolar, i.e., they showed single positive and negative regions. For patients with VT, the extrema were either distant, with one over the precordial area and the other over the back, or close together in the precordial region. In 10 patients, maps recorded after administration of antiarrhythmic drugs remained the same while QRS duration was prolonged. In six patients, maps recorded before antiarrhythmic surgery showed distant extrema for septal or posterobasal VT sites of origin and close extrema for anterior or posteroapical sites. Generally, QRS duration was reduced and maps were modified after surgery. Late potentials can be well detected with only three orthogonal leads because their distributions are dipolar, but maps provide additional information about their distribution, which may be related to conduction delay sites and possibly to VT sites of origin. Sources near the torso surface would produce close extrema, whereas deeper sources would produce distant extrema.
Vest inflation without simultaneous ventilation during cardiac arrest in dogs: improved survival from prolonged cardiopulmonary resuscitation.
Authors: Halperin H R , Guerci A D , Chandra N , Herskowitz A , Tsitlik J E , Niskanen R A , Wurmb E , Weisfeldt M L
Published: June 2011

Myocardial and cerebral blood flow can be generated during cardiac arrest by techniques that manipulate intrathoracic pressure. Augmentation of intrathoracic pressure by high-pressure ventilation simultaneous with compression of the chest in dogs has been shown to produce higher flows to the heart and brain, but has limited usefulness because of the requirement for endotracheal intubation and complex devices. A system was developed that can produce high intrathoracic pressure without simultaneous ventilation by use of a pneumatically cycled vest placed around the thorax (vest cardiopulmonary resuscitation [CPR]). The system was first tested in a short-term study of the maximum achievable flows during arrest. Peak vest pressures up to 380 mm Hg were used on eight 21 to 30 kg dogs after induction of ventricular fibrillation and administration of epinephrine. Microsphere-determined myocardial blood flow was 108 +/- 17 ml/min/100 g (100 +/- 16% of prearrest flow) and cerebral flow was 51 +/- 12 ml/min/100 g (165 +/- 39% of prearrest). Severe lung or liver trauma was noted in three of eight dogs. If peak vest pressure was limited to 280 mm Hg, however, severe trauma was no longer observed. A study of the hemodynamics during and survival from prolonged resuscitation was then performed on three groups of seven dogs. Vest CPR was compared with manual CPR with either conventional (300 newtons) or high (430 newtons) sternal force. After induction of ventricular fibrillation, each technique was performed for 26 min. Defibrillation was then performed.(ABSTRACT TRUNCATED AT 250 WORDS)
Regional and global left ventricular function in infants with anomalous origin of the left coronary artery from the pulmonary trunk: preoperative and postoperative assessment.
Authors: Rein A J , Colan S D , Parness I A , Sanders S P
Published: June 2011

Anomalous origin of the left coronary artery from the pulmonary trunk (ALCA) remains a diagnostic as well as a therapeutic problem. The purposes of this study were: (1) to analyze left ventricular mechanics, including regional wall motion, in infants with ALCA, (2) to determine if the pattern of wall motion in infants with ALCA distinguishes these patients from those with congestive cardiomyopathy of other causes, and (3) to evaluate the potential for recovery of left ventricular function after successful restoration of a dual coronary artery system. Left ventricular mechanics were studied before and serially after surgery in six infants (2 to 13 months old) with ALCA. Fifteen age-matched normal subjects and seven age-matched patients with idiopathic congestive cardiomyopathy were also studied for comparison. Preoperatively, the end-diastolic volume in infants with ALCA was about four times larger than normal and did not differ from that in infants with CM; the myocardial volume was also about three times larger than normal, similar to that in the patients with CM. The myocardial volume/end-diastolic volume ratio was extremely low in patients with ALCA and in those with CM. The infants with ALCA did not exhibit specific segmental wall motion abnormalities but rather had global hypokinesis indistinguishable from that in the patients with CM. After successful repair, end-diastolic volume index rapidly decreased, reaching near normal values by 7 to 22 months after surgery, while myocardial volume index decreased at a slower rate, leading to an early phase of "overshoot hypertrophy," but reaching normal values by 7 to 22 months after surgery.+
Fibrinopeptide A and platelet factor levels in unstable angina pectoris.
Authors: Théroux P , Latour J G , Léger-Gauthier C , De Lara J
Published: June 2011

Fibrinopeptide A, platelet factor 4, beta-thromboglobulin, thromboxane B2, and 6-keto-prostaglandin F1 alpha were estimated by radioimmunoassay on venous plasma samples taken within 48 hr of admission from 16 consecutive patients with unstable angina and 15 patients with stable angina matched for clinical variables. The ratio of circulating platelet aggregates, platelet aggregation to increasing concentrations of ADP (0.455 to 1.82 micrograms/ml), and platelet thromboxane B2 production in vitro were also tested. The two groups of patients were statistically similar in terms of sex distribution, age, presence of risk factors, use of medication, extent of coronary artery disease and history of previous myocardial infarction. Mean plasma levels of fibrinopeptide A were 2.7 +/- 0.4 ng/ml (geometric means +/- SEM, range 1.5 to 5.5) in patients with stable angina vs 5.5 +/- 1.8 ng/ml (range 2.4 to 32; p less than .001) in those with unstable angina. In the latter group, after 6 to 8 days, fibrinopeptide A levels decreased to 3.6 +/- 0.5 ng/ml (range 1.5 to 9.3; p less than .04 vs admission). All other variables measured were statistically identical in the two groups. We conclude that plasma fibrinopeptide A levels, as opposed to platelet factors, discriminate between patients with unstable and stable angina, indicating an activation of the coagulation system in unstable angina.
Assessment of left ventricular and aortic valve function after aortic balloon valvuloplasty in adult patients with critical aortic stenosis.
Authors: McKay R G , Safian R D , Lock J E , Diver D J , Berman A D , Warren S E , Come P C , Baim D S , Mandell V E , Royal H D
Published: June 2011

Preliminary reports have documented the utility of balloon aortic valvuloplasty as a palliative treatment for high-risk patients with critical aortic stenosis, but the effect of this procedure on cardiac performance has not been studied in detail. Accordingly, 32 patients (mean age 79 years) with long-standing, calcific aortic stenosis were treated at the time of cardiac catheterization with balloon dilatation of the aortic valve, and serial changes in left ventricular and valvular function were followed before and after valvuloplasty by radionuclide ventriculography, determination of systolic time intervals, and Doppler echocardiography. Prevalvuloplasty examination revealed heavily calcified aortic valves in all patients, a mean peak-to-peak aortic valve gradient of 77 +/- 27 mm Hg, a mean Fick cardiac output of 4.6 +/- 1.4 liters/min, and a mean calculated aortic valve area of 0.6 +/- 0.2 cm2. Subsequent balloon dilatation with 12 to 23 mm valvuloplasty balloons resulted in a fall in aortic valve gradient to 39 +/- 15 mm Hg, an increase in cardiac output to 5.2 +/- 1.8 liters/min, and an increase in calculated aortic valve area to 0.9 +/- 0.3 cm2. Individual hemodynamic responses varied considerably, with some patients showing major increases in valve area, while others demonstrated only small increases. In no case was balloon dilatation accompanied by evidence of embolic phenomena. Supravalvular aortography obtained in 13 patients demonstrated no or a mild (less than or equal to 1+) increase in aortic insufficiency. Serial radionuclide ventriculography in patients with a depressed left ventricular ejection fraction (i.e., that less than or equal to 55%) revealed a small increase in ejection fraction from 40 +/- 13% to 46 +/- 12% (p less than .03). In addition, for the study group as a whole there was a decrease in left ventricular end-diastolic volume index (113 +/- 38 to 101 +/- 37 ml/m2, p less than .003), a fall in stroke-volume ratio (1.49 +/- 0.44 to 1.35 +/- 0.33, p less than .04), and no immediate change in left ventricular peak filling rate (2.05 +/- 0.77 to 2.21 +/- 0.65 end-diastolic counts/sec, p = NS). Serial M mode echocardiography and phonocardiography showed an increase in aortic valve excursion (0.5 +/- 0.2 to 0.8 +/- 0.2 cm, p less than .001), a decrease in time to one-half carotid upstroke (80 +/- 30 to 60 +/- 10 msec, p less than .001), and a small decrease in left ventricular ejection time (0.44 +/- 0.03 to 0.42 +/- 0.02 sec, p less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)
Delayed myocardial ischemia induced by anger.
Authors: Verrier R L , Hagestad E L , Lown B
Published: June 2011

The objectives of this study were to develop a reproducible behavioral model that simulates the anger state and to characterize its influence on myocardial blood flow in both the normal and compromised coronary circulations. Fourteen mongrel dogs of both sexes were studied. The animals were instrumented for the recording of electrocardiogram, arterial blood pressure, and left circumflex coronary arterial blood flow. A critical level of coronary stenosis was achieved with an adjustable occluder placed just distal to the flow probe. Anger was induced in the instrumented animals by having another dog challenge their access to food. In the absence of coronary artery stenosis, provocation of anger increased heart rate from 107 +/- 6 to 215 +/- 15 beats/min, arterial blood pressure from 95 +/- 4 to 142 +/- 5 mm Hg, and coronary blood flow from 31 +/- 5 to 72 +/- 9 ml/min. These variables returned to the preanger levels within 2 to 4 min. Induction of anger was repeated after a critical stenosis was applied to the left circumflex coronary artery. Anger increased heart rate from 112 +/- 6 to 210 +/- 16 beats/min, arterial blood pressure from 99 +/- 3 to 142 +/- 6 mm Hg, and coronary arterial flow from 23 +/- 5 to 35 +/- 7 ml/min. Within 2 to 4 min after the bout of anger, all dogs exhibited significant reductions in coronary arterial flow (35% of baseline; p less than .001), increases in coronary vascular resistance (557% of baseline; p less than .002), and ischemic ST segment changes in leads II, III, and aVF.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular adaptations to intense swim training in sedentary middle-aged men and women.
Authors: Martin W H , Montgomery J , Snell P G , Corbett J R , Sokolov J J , Buckey J C , Maloney D A , Blomqvist C G
Published: June 2011

Central and peripheral cardiovascular adaptations to 12 weeks of intense swim training were characterized in 12 previously sedentary middle-aged men and women. Peak oxygen uptake (VO2) during upright bicycle exercise improved from 29.2 +/- 5.6 to 34.7 +/- 6.7 ml/kg/min (mean +/- SD, p less than .01) because of similar increases in peak cardiac output (CO) and calculated arteriovenous oxygen difference (both p = .02). Peak supine VO2 was 10% higher after training (p less than .005) solely because of enhanced CO (p = .005). Peak heart rate decreased in both postures; therefore stroke volume at peak exercise was greater by 10% and 18% in the upright and supine postures, respectively (p = .05 and p = .005). There was an identical 18% rise (p = .01) in peak supine left ventricular end-diastolic volume index by radionuclide ventriculography but no change in left ventricular ejection fraction or end-systolic volume index (ESVI). Peak systolic blood pressure (SBP) was unchanged in the upright posture but was 8% higher (p = .002) during recumbency despite a similar total peripheral resistance and SBP/ESVI ratio. Maximal calf conductance (Gmax), assessed separately by venous occlusion plethysmography after local ischemic exercise to fatigue, was augmented 20% (p less than .02) by training, resulting in an 18% greater hyperemic blood flow (p = .05). Peak VO2, CO, and Gmax were unchanged in five nonexercising control subjects. We conclude that in middle-aged humans, intense swim training for 12 weeks produces adaptations that include a greater capacity for vasodilatation in skeletal muscle and an enhanced cardiac pump capacity.
Deficient production of cyclic AMP: pharmacologic evidence of an important cause of contractile dysfunction in patients with end-stage heart failure.
Authors: Feldman M D , Copelas L , Gwathmey J K , Phillips P , Warren S E , Schoen F J , Grossman W , Morgan J P
Published: June 2011

We studied the effects of different classes of inotropic drugs on human working myocardium in vitro that was isolated from the hearts of patients with end-stage heart failure, and compared the responses to these drugs with those noted in muscles from nonfailing control hearts. Although peak isometric force generated in response to increased extracellular calcium reached control levels in the muscles from patients with heart failure, the time course of contraction and rate of relaxation were greatly prolonged. The inotropic effectiveness of the beta-adrenergic agonist isoproterenol and the phosphodiesterase inhibitors milrinone, caffeine, and isobutylmethylxanthine was markedly reduced in muscles from the patients with heart failure. In contrast, the effectiveness of inotropic stimulation with acetylstrophanthidin and the adenylate cyclase activator forskolin was preserved. After a minimally effective dose of forskolin was given to elevate intracellular cyclic AMP levels, the inotropic responses of muscles from the failing hearts to phosphodiesterase inhibitors were markedly potentiated. These data indicate that an abnormality in cyclic AMP production may be a fundamental defect present in patients with end-stage heart failure that can markedly diminish the effectiveness of agents that depend on generation of this nucleotide for production of a positive inotropic effect.
Monophasic action potential mapping in human subjects with normal electrocardiograms: direct evidence for the genesis of the T wave.
Authors: Franz M R , Bargheer K , Rafflenbeul W , Haverich A , Lichtlen P R
Published: June 2011

T wave concordance in the normal human electrocardiogram (ECG) generally is explained by assuming opposite directions of ventricular depolarization and repolarization; however, direct experimental evidence for this hypothesis is lacking. We used a contact electrode catheter to record monophasic action potentials (MAPs) from 54 left ventricular endocardial sites during cardiac catheterization (seven patients) and a new contact electrode probe to record MAPs from 23 epicardial sites during cardiac surgery (three patients). All patients had normal left ventricular function and ECGs with concordant T waves. MAP recordings during constant sinus rhythm or right atrial pacing were analyzed for activation time (AT) = earliest QRS deflection to MAP upstroke, action potential duration (APD) = MAP upstroke to 90% repolarization, and repolarization time (RT) = AT plus APD. AT and APD varied by 32 and 64 msec, respectively, over the left ventricular endocardium and by 55 and 73 msec, respectively, over the left ventricular epicardium. On a regional basis, the diaphragmatic and apicoseptal endocardium had the shortest AT and the longest APD, and the anteroapical and posterolateral endocardium had the longest AT and the shortest APD (p less than .05 to less than .0001). RT was less heterogeneous than APD, and no significant transventricular gradients of RT were found. In percent of the simultaneously recorded QT interval, epicardial RT ranged from 70.8 to 87.4 (mean 80.7 +/- 3.9) and endocardial RT ranged from 80 to 97.8 (mean 87.1 +/- 4.4) (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Circadian variation of transient myocardial ischemia in patients with coronary artery disease.
Authors: Rocco M B , Barry J , Campbell S , Nabel E , Cook E F , Goldman L , Selwyn A P
Published: June 2011

To examine whether a significant circadian variation of transient myocardial ischemia exists and to better understand the character of such variation, 32 patients with chronic stable symptoms of coronary artery disease underwent one or more days of ambulatory monitoring of ischemic ST segment changes during daily life. A total of 251 episodes of ischemic ST segment depression occurred in 24 (75%) of the 32 patients with a median duration of 5 min (range 1 to 253). A significant circadian increase in ischemic activity was found with 39% of episodes and 46% of total ischemic time occurring between 6 A.M. and 12 P.M. (p less than .05 and p = .02, respectively). In 21 patients with ST segment depression during the 6 hr after waking and the 6 hr before sleep, 68% of episodes occurred in the morning compared with 32% in the evening. There were no significant differences in heart rate at onset, heart rate at 1 min before onset, and activity score associated with ST segment depression. The proportion of minutes showing ST segment depression when the heart rate was above the lowest rate associated with ST segment depression was significantly greater in the morning compared with the evening (26% vs 15%; p = .03). Thus the early morning increase in ST segment depression does not appear to be explained by differences in extrinsic activity and/or stress measured by physical activity score and heart rate response. More importantly, this phenomenon is often ignored by the usual patterns of drug administration for angina.(ABSTRACT TRUNCATED AT 250 WORDS)
Interobserver variability in the pathologic interpretation of endomyocardial biopsy results.
Authors: Shanes J G , Ghali J , Billingham M E , Ferrans V J , Fenoglio J J , Edwards W D , Tsai C C , Saffitz J E , Isner J , Furner S
Published: June 2011

Controversy exists over the role of endomyocardial biopsy in evaluating patients with dilated cardiomyopathy, particularly in detecting myocarditis and in assessing prognosis. Interobserver variability, if high, could explain conflicting reports. To assess this possibility, we submitted biopsy specimens from 16 patients with dilated cardiomyopathy to seven cardiac pathologists. The same slides were independently reviewed by each and assessed for fibrosis, hypertrophy, nuclear changes on a 0 to 3+ scale, mean lymphocyte count per high-power field, and myocarditis. The prevalance of significant fibrosis ranged from 25% to 69%, hypertrophy from 19% to 88%, nuclear changes from 31% to 94%, and abnormal lymphocyte count from 0 to 38%. One or more pathologists diagnosed definite or possible myocarditis in 11 of the 16 patients. Of these 11 patients, three pathologists agreed about three and two pathologists agreed about five. Myocarditis was diagnosed by a single pathologist in three cases. We conclude that interobserver variability is high in interpreting biopsy specimens from patients with dilated cardiomyopathy and that quantitative and standardized methods are needed to increase diagnostic consistency.
Attenuation of exercise-induced myocardial ischemia in dogs with recruitment of coronary vasodilator reserve by nifedipine.
Authors: Heusch G , Guth B D , Seitelberger R , Ross J
Published: June 2011

There is now evidence that under resting conditions coronary vasodilator reserve exists even in the presence of myocardial ischemia. Therefore, we tested the hypothesis that a vasodilator reserve may exist during exercise so that during exercise-induced ischemia a reduction in coronary constrictor tone can be produced that attenuates the decreases in regional myocardial blood flow and function distal to a severe coronary stenosis without changing the determinants of myocardial oxygen demand. Nine dogs were instrumented with an ameroid constrictor on the left circumflex coronary artery and were studied 2 to 3 weeks later. During a control treadmill run, heart rate increased from 119 +/- 20 to 225 +/- 20 beats/min and peak left ventricular pressure increased from 144 +/- 17 to 163 +/- 28 mm Hg. Poststenotic subendocardial blood flow (measured by a microsphere technique) fell from 1.19 +/- 0.36 to 0.51 +/- 0.30 ml/min X g and systolic wall thickening (by sonomicrometry) decreased from 24.3 +/- 5.8% to 6.0 +/- 6.1%. During an identical run after nifedipine (10 micrograms/kg iv), systemic hemodynamics were not significantly altered. However, subendocardial blood flow was increased to 0.85 +/- 0.51 ml/min X g (p less than .05) and systolic wall thickening to 11.4 +/- 7.8% (p less than .01). We conclude that in this study the amelioration of exercise-induced myocardial ischemia was due to the recruitment by nifedipine of coronary vasodilator reserve.
Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.
Authors: Dhainaut J F , Huyghebaert M F , Monsallier J F , Lefevre G , Dall'Ava-Santucci J , Brunet F , Villemant D , Carli A , Raichvarg D
Published: June 2011

To investigate disturbances in the coronary circulation and myocardial metabolism during septic shock, we examined coronary sinus blood flow and myocardial substrate extraction in 40 patients with septic shock and 13 control patients. Patients with coronary artery disease were excluded from this study. The global hemodynamic pattern of the septic patients was characterized by a lower stroke volume, despite an elevated cardiac index. Coronary sinus blood flow was high (187 +/- 47 vs 130 +/- 21 ml/min in the control group, p less than .001) due to marked coronary vasodilation, especially in the subgroup of nonsurvivors. In contrast to the control group, myocardial lactate uptake was elevated, while that of free fatty acids, glucose, and ketone bodies was diminished in patients with septic shock. These findings were especially prominent in the nonsurvivors. Expressed as oxygen equivalents, the contribution of free fatty acids as an energy source of the myocardium was markedly diminished in septic patients (12% vs 54% in the control group, p less than .005), while that of lactate was increased (36% vs 12%, p less than .01). The observed shift in myocardial substrate extraction was associated with a discrepancy between measured myocardial oxygen consumption and that calculated chemically from commonly available exogenous substrates: 41% of myocardial oxygen consumption was not explained by the utilization of commonly available substrates extracted from coronary circulation in all patients with septic shock.(ABSTRACT TRUNCATED AT 250 WORDS)
Prenatal diagnosis and postnatal management of critical aortic stenosis.
Authors: Huhta J C , Carpenter R J , Moise K J , Deter R L , Ott D A , McNamara D G
Published: June 2011

Fetal echocardiography has yet to have an impact on the treatment of congenital heart disease. Critical aortic valve stenosis was diagnosed by echocardiography before birth in a 35 week gestation fetus. The risks to the fetus and mother associated with prolonged rupture of membranes prompted their transport to a hospital with cardiac surgical and high-risk perinatal facilities. Prenatal and postnatal echocardiographic findings agreed regarding the diagnostic criteria for critical aortic stenosis and primary forms of cardiomyopathy were excluded. Results of fetal Doppler examination were consistent with valvular aortic stenosis and excluded mitral regurgitation. Determination of the left ventricular size excluded ventricular hypoplasia. The infant was delivered by cesarean section and underwent successful emergency aortic valvotomy at 12 h of age. Fetal echocardiography, in combination with a multidisciplinary postnatal approach, can be used in the successful treatment of a severe form of congenital heart disease.
Long-term results after the Fontan operation for tricuspid atresia.
Authors: Girod D A , Fontan F , Deville C , Ottenkamp J , Choussat A
Published: June 2011

Between 1968 and 1977, 32 patients who underwent the Fontan operation for tricuspid atresia at Bordeaux, France, or Leiden, The Netherlands, survived at least 1 year after surgery. These patients were evaluated clinically 7 to 16 years (mean 8.9 years) after surgery by review of clinical records, questionnaire, or direct examination. There were five deaths: one during arrhythmia, the second sudden and unexplained, and three others after reoperation. Four of the five patients had evidence of obstruction of the atriopulmonary or atrioventricular conduit. There were eight reoperations. Two were for residual atrial septal defects, one for an atrial septal defect and an intrapulmonary arteriovenous fistula, and one for a residual ventricular septal defect. The other four were reoperated for severe conduit or homograft obstruction. One of these four also had a residual shunt, severe mitral regurgitation, and reduced left ventricular function. One patient was found to have left ventricular dysfunction 3 months after surgery, which persisted. Another patient had left ventricular dysfunction unmasked after successful mitral annuloplasty for severe mitral regurgitation. No other patients had clinical evidence of left ventricular dysfunction. Recurrent supraventricular tachycardia occurred in four patients and was eventually fatal in one patient with associated conduit obstruction. Of the 27 survivors, 13 are in NYHA class I, 13 are in class II, and one is in class III. We conclude that clinical results of the Fontan operation remain good in most patients 7 to 16 years after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential structural responses of small resistance vessels to antihypertensive therapy.
Authors: Sano T , Tarazi R C
Published: June 2011

Regression of left ventricular hypertrophy after control of blood pressure has been documented with some antihypertensive agents but not with others. To determine whether similar differences in regression of wall thickening also occur in resistance vessels during treatment, matched groups of spontaneously hypertensive rats (SHR) were treated for 12 weeks with either hydralazine (H) or captopril and hydrochlorothiazide (C-D) and they were compared with untreated SHR and Wistar-Kyoto rats (WKY). Perfusion pressure was then determined in the hindlimbs of pithed rats under conditions of constant blood flow (4.0 ml/min) and maximal vasodilation (hemodilution to 22% hematocrit combined with continuous nitroprusside and papaverine infusion). This perfusion pressure, which has been validated as an index of thickening (hypertrophy) of resistance vessels walls, averaged 26.8 +/- 0.4(SE) mm Hg in untreated WKY (n = 12) and 37.6 +/- 0.4 mm Hg in untreated SHR (n = 11) (p less than .01). Treatment with H or C-D controlled blood pressure equally in SHR, but the two drugs had significantly different effects on both left ventricular hypertrophy and resistance vessels. Perfusion pressure was reduced from 37.6 +/- 0.4 mm Hg to 34.0 +/- 0.5 mm Hg (p less than .01) with C-D but only to 36.5 +/- 0.5 mm Hg with H (NS). Left ventricular weight was significantly reduced by C-D (2.02 +/- 0.02 vs 2.63 +/- 0.05 mg/g, p less than .01) but only to 2.44 +/- 0.05 mg/g by H.(ABSTRACT TRUNCATED AT 250 WORDS)
Prediction of the physiologic significance of coronary arterial lesions by quantitative lesion geometry in patients with limited coronary artery disease.
Authors: Wilson R F , Marcus M L , White C W
Published: June 2011

Studies in animals with normal coronary arteries have shown that coronary flow reserve can be predicted by angiographic measurements of arterial stenosis. Studies in man, however, suggest that even quantitative analysis of coronary angiograms cannot predict the physiologic significance of individual coronary lesions. These studies, however, were carried out in patients with either widespread, diffuse coronary artery disease or by measurement techniques that tend to underestimate maximal coronary flow reserve. To determine the relationship between coronary arterial stenosis and coronary flow reserve (CFR) in patients with discrete limited coronary atherosclerosis, we studied 50 patients with a single discrete coronary stenosis in only one or two vessels. The minimum coronary arterial cross-sectional area (mCSA), percent area stenosis (%AS), and percent diameter stenosis in the left and right anterior oblique projections were determined by the Brown/Dodge method of quantitative coronary angiography. A No. 3F coronary Doppler catheter was placed immediately proximal to the lesion. Measurements of CFR were obtained by intracoronary administration of papaverine in doses sufficient to provide maximal arteriolar vasodilation. In 25 patients, a translesional pressure gradient was obtained with an angioplasty catheter. CFR measured in patients with coronary artery disease was compared with that in 13 patients with normal coronary vessels. In normal patients, CFR averaged 5.0 +/- 0.6 (peak/resting velocity ratio; mean +/- SEM, range 3.7 to 8.2). In patients with limited coronary artery disease, CFR was closely correlated with %AS (r = .85), mCSA (r = .79), and the translesional pressure gradient (r = .83). Additionally, the most severe percent diameter stenosis in either the left or right anterior oblique view was also highly correlated with CFR (r = .82). Importantly, all arteries with lesions producing less than 70% area stenosis and less than 50% diameter stenosis, or with greater than 2.5 mm2 mCSA had CFR of over 3.5. These results suggest that, in contrast to the poor correlation of percent area and percent diameter stenosis to CFR measured in patients with multivessel coronary artery disease, CFR measured at angiography in patients with discrete, limited coronary artery disease correlates closely with luminal stenosis determined precisely with quantitative coronary angiography. Differences in the extent of diffuse arterial narrowing may account for these discrepancies.
Atrioventricular block in posterior acute myocardial infarction: a clinicopathologic correlation.
Authors: Bilbao F J , Zabalza I E , Vilanova J R , Froufe J
Published: June 2011

The specialized conducting systems of 44 hearts with posterior-inferior acute myocardial infarction were studied to clarify the anatomic basis of atrioventricular (AV) block. The results showed a lack of correlation between the block and the lesional pathology of the specialized conducting system. On the other hand, an evaluation of the atrial prenodal myocardium revealed strong clinicopathologic correlation between the block and the necrotic damage to these fibers. Twenty-nine or 97% of patients with AV block showed acute necrosis of the prenodal atrial myocardium. Considering the conducting prenodal septal atrial myocardium as a suprahisian structure, the necrosis at this level would provide an anatomic basis of the block in posterior-inferior acute myocardial infarction. Analysis of the behavior of the AV block after pharmacologic treatment further established a relationship between the block and acute lesions in the central conduction system.
Potentiation of cardiac electrophysiologic effects of verapamil after autonomic blockade or cardiac transplantation.
Authors: Qi A Z , Tuna I C , Gornick C C , Barragry T P , Blatchford J W , Ring W S , Bolman R M , Walker M J , Benditt D G
Published: June 2011

Cardiac electrophysiologic effects of verapamil in vivo are the result of both direct and indirect actions on the heart (the latter due to augmentation of sympathetic neural tone, diminution of parasympathetic neural tone, and increased circulating catecholamines). In this study we assessed the interaction of verapamil's direct and indirect actions on electrophysiologic properties of the heart in awake, previously instrumented, unsedated dogs. After administration of intravenous verapamil (0.2 mg/kg), electrophysiologic effects were assessed serially over a 1 hr period in 10 awake dogs before (group 1 studies) and during pharmacologic autonomic blockade (group 2 studies), and in a subset of these dogs (n = 5) after orthotopic cardiac transplantation (group 3 studies). In group 1 dogs, sinus cycle length (SCL) initially shortened after verapamil (postverapamil 379 +/- 50 msec vs baseline of 494 +/- 72 msec, p less than .001) and subsequently gradually prolonged. In groups 2 and 3, transient SCL shortening was absent. SCL prolonged promptly after verapamil, and sinus arrest developed in two of 10 group 2 and two of five group 3 animals. Verapamil exerted a negative dromotropic effect on atrioventricular node conduction in all three experimental groups, as assessed by drug-induced changes in minimum cycle length with sustained 1:1 atrioventricular conduction and measurements of atrioventricular node effective and functional refractory period. However, compared with findings in group 1, this negative dromotropic effect occurred more rapidly and was markedly potentiated in groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)