bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation of cardiac surface QRST distributions to ventricular fibrillation threshold in dogs.
Authors: Kubota I , Lux R L , Burgess M J , Abildskov J A
Published: June 2011

The relation between ventricular fibrillation threshold (VFT) and cardiac surface QRST area distributions was studied in eight pentobarbital-anesthetized dogs. Unipolar epicardial electrograms were recorded from 64 sites evenly distributed on the right and left ventricles. Localized areas of short repolarization properties were produced by directing five intensities of light onto the surface of the anterior right ventricle through apertures of three sizes. VFT, measured at the center of the lesion, decreased during warming and had a high negative correlation to the change (warming-control) in QRST area (delta QRST1) in the electrogram recorded from the center of the lesion. This correlation was independent of lesion size. For the six experiments, the correlation coefficients for 400-, 800-, and 1,600-mm2 lesions averaged -0.95, -0.94, and -0.96, respectively. The correlation between VFT and delta QRST1 without regard to lesion size averaged -0.88. VFT also had a negative correlation to root mean square (RMS)delta QRST because of warming. RMS delta QRST was calculated from the change in QRST areas (warming-control) in all 64 electrograms. The correlation between VFT and RMS delta QRST was dependent on lesion size. For all experiments, the correlation between VFT and RMS delta QRST averaged -0.97, -0.93, and -0.93 for 400-, 800-, and 1,600-mm2 lesions, respectively. The correlation between VFT and RMS delta QRST without regard to lesion size, however, was considerably lower, -0.59. The results of this study provide the first direct evidence that VFT is correlated with cardiac surface QRST area distributions.
Cellular mechanisms of myocardial infarct expansion.
Authors: Weisman H F , Bush D E , Mannisi J A , Weisfeldt M L , Healy B
Published: June 2011

Infarct expansion is acute regional dilatation and thinning of the infarct zone. There are several possibilities for the mechanism of this alteration in cardiac shape: thinning could be caused by 1) cell rupture, 2) a reduction in the intercellular space, or 3) stretching of myocytes or 4) slippage of groups of myocytes so that less cells are distributed across the wall. To determine the relative contributions of these cellular mechanisms of wall thinning and dilatation, detailed study of transverse histological sections of rat hearts with infarct expansion was performed 1, 2, and 3 days after coronary ligation. The number of cells across the wall was determined in six regions within, adjacent to, and remote from the infarct. Cell counting was performed so that the total number of cells across the wall and the number of cells per unit length (cell density) across the wall were determined. The transmural cell count and the cell density were correlated with the wall thickness in each region. Myocyte cross-sectional areas and sarcomere lengths were also measured. The results from the infarct expansion hearts were compared with those of sham-operated control hearts that had been similarly analyzed. To ensure that mechanisms identified in the rat were applicable to human infarct expansion, five hearts from patients who died within 3 days of infarction and two hearts from patients without coronary disease were studied histologically in a similar fashion. Wall thinning occurred in all regions of the rat infarct expansion hearts compared with controls (p less than 0.0001) but, as expected, was most pronounced in the infarct zone. A decrease in the number of cells across the wall accompanied the wall thinning at each site (p less than 0.0001), and this change in cell number was highly correlated with the changes in wall thickness (r = 0.915, p less than 0.001). Cell density increased from controls only within the infarct zone (p less than 0.001) and accounted for at most 20% of the thinning in that region. The change in cell density was attributable to both cell stretch (measured by increased sarcomere length and decreased myocyte cross-sectional area) and a decrease in the intercellular space. A similar strong correlation between wall thinning and decreased number of cells across the wall was identified in the human hearts (r = 0.94, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of effects of three anesthetic agents on induction of ventricular tachycardia in a canine model of myocardial infarction.
Authors: Hunt G B , Ross D L
Published: June 2011

The effects of three anesthetic agents on the inducibility of ventricular tachycardia by programmed stimulation were investigated in dogs with a surgically induced left ventricular infarct. Endocardial catheter electrodes were placed at the right ventricular apex under general anesthesia at least 2 weeks after infarction, and the dogs were allowed to recover for 24 hours before undergoing programmed stimulation in the conscious state on two occasions 2 hours apart. A protocol of programmed stimulation with up to seven ventricular extrastimuli was used. In 15 animals, ventricular tachycardia was inducible on both occasions with 3.4 +/- 0.4 (mean +/- SEM; range, 1-5) extrastimuli. Two hours after baseline conscious induction, the dogs were anesthetized with either halothane, pentobarbital, or a fixed combination of fentanyl-droperidol plus nitrous oxide. Halothane prolonged the PR interval from 99 +/- 4 to 117 +/- 6 msec (p = 0.001) and the ventricular effective refractory period from 140 +/- 4 to 157 +/- 6 msec (p = 0.008). The ability to induce ventricular tachycardia was abolished in five of 10 animals (p less than 0.05). In the animals that remained inducible, the cycle length of tachycardia increased from 153 +/- 10 to 168 +/- 10 msec (p = 0.015), while the number of extrastimuli required was unaltered. Pentobarbital prolonged the PR interval from 104 +/- 6 to 124 +/- 6 msec (p = 0.004) and the QTc interval from 270 +/- 10 to 310 +/- 6 msec (p = 0.006). Ventricular tachycardia remained inducible in only six of 10 dogs (p less than 0.05) with no change in cycle length or the number of extrastimuli required. Ventricular fibrillation was inducible in an additional three dogs with a number of extrastimuli similar to that required to induce ventricular tachycardia before anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Morning increase in platelet aggregability. Association with assumption of the upright posture.
Authors: Brezinski D A , Tofler G H , Muller J E , Pohjola-Sintonen S , Willich S N , Schafer A I , Czeisler C A , Williams G H
Published: June 2011

The frequencies of onset of myocardial infarction and sudden cardiac death are increased between 6 AM and 12 noon. Platelet aggregability, which may play a role in the cause of these disorders, has been observed to increase after the normal morning activities of awakening, arising, and ambulating. To determine which morning activity or activities are responsible for this aggregability increase, we measured platelet aggregation in 16 normal subjects on a control day of delayed arising (i.e., subjects remained supine until 12:30 PM) and on a day in which normal morning activities were divided into three isolated components of awakening (8 AM), assumption of upright posture (9:30 AM), and ambulating (11 AM). Blood samples to assess platelet aggregability were drawn at 8 AM before activity and 90 minutes after the initiation of each activity (i.e., at 9:30 AM, 11 AM, and 12:30 PM). For the group, in vitro platelet responsiveness to adenosine diphosphate and epinephrine increased only after assumption of the upright posture. The lowest concentration of agonist required to produce biphasic platelet aggregation decreased (aggregability increased) between 9:30 and 11 AM (90 minutes after assumption of the upright posture) from 3.3 +/- 0.3 to 2.4 +/- 0.2 microM for adenosine diphosphate (p less than 0.05) and from 2.1 +/- 0.5 to 1.0 +/- 0.4 microM for epinephrine (p less than 0.05). During the same interval, plasma epinephrine increased from 34 +/- 7 to 55 +/- 9 pg/ml (p less than 0.05), and plasma norepinephrine increased from 169 +/- 19 to 298 +/- 25 pg/ml (p less than 0.01). There was no significant change in aggregability or catecholamine concentrations on the control day.(ABSTRACT TRUNCATED AT 250 WORDS)
In vivo measurement of neuronal uptake of norepinephrine in the human heart.
Authors: Goldstein D S , Brush J E , Eisenhofer G , Stull R , Esler M
Published: June 2011

Neuronal uptake (Uptake-1) of the sympathetic neurotransmitter norepinephrine from the circulation in the human heart was assessed in vivo with three techniques. 1) Cardiac removal of intravenously infused tracer-labeled norepinephrine was measured before and after Uptake-1 blockade with desipramine; 2) the difference between the fractional extraction of radioactive norepinephrine and of radioactive isoproterenol, which is not a substrate for neuronal uptake, was used to estimate the removal of norepinephrine by Uptake-1 in the heart compared with other vascular beds (arm, leg, brain, and lungs); and 3) regional arteriovenous differences in radioactive and endogenous dihydroxyphenylglycol (DHPG), an exclusively intraneuronal metabolite of norepinephrine, were compared in these beds. In untreated patients, cardiac removal of radioactive norepinephrine averaged 79%, whereas in desipramine-treated patients, cardiac removal of radioactive norepinephrine averaged 19%, a value similar to that of isoproterenol in untreated patients (14%), confirming that in the heart the non-neuronal removals of isoproterenol and norepinephrine were similar. In the heart, 69% of delivered norepinephrine was estimated to be removed by Uptake-1, a much higher percentage than that in the arm (14%), leg (7%), brain (10%), and lungs (4%). The cardiac arteriovenous increment in endogenous DHPG (137%) far exceeded that of the other beds (49%, 26%, 39%, and -19%, respectively), and radioactive DHPG in the great cardiac vein exceeded arterial levels by 113%, whereas in the other beds, arterial radioactive DHPG exceeded venous levels. The results indicate that the human heart is exceptionally dependent on neuronal uptake for in vivo removal of circulating norepinephrine.
Changes in spontaneous variability of ventricular ectopic activity as a function of time in patients with chronic arrhythmias.
Authors: Anastasiou-Nana M I , Menlove R L , Nanas J N , Anderson J L
Published: June 2011

Previous determinations of spontaneous variability in ventricular arrhythmia have often been based on measurements from consecutive days in small patient populations, whereas clinical determinations of drug efficacy typically compare measurements at intervals of 1 week and longer to baseline. We, therefore, sought to determine whether spontaneous arrhythmia variability changes as a function of time during periods ranging from 1 day to 1 year or longer. The percent reduction in the frequency of total premature ventricular complexes (PVCs) and repetitive ventricular beats required to show true drug effect rather than spontaneous variability in PVCs was determined in 47 consecutive patients with chronic ventricular arrhythmias who underwent multiple ambulatory monitor recordings while off active drug treatment (during placebo therapy). The variability in PVC rate was determined during the intervals of 1 day, 1 week, 2 weeks, 3 weeks, 4 weeks, and 1 year or longer. The percent reductions in total PVCs required to exceed the 95% confidence limits of spontaneous variability at these intervals were 55%, 85%, 86%, 93%, 96%, and 96%, respectively. Corresponding values for repetitive beats were 75%, 95%, 92%, 95%, 94%, and 98%, respectively. The percent increase in total PVCs and repetitive beats required to establish "arrhythmia aggravation" caused by an antiarrhythmic drug with a 95% confidence limit also was calculated for this study population and was 124% and 303%, respectively, at 1-day intervals and 2,269% and 4,091%, respectively, at 1-year (or longer) intervals for the 24-hour monitor recordings. Variability was not substantially affected by underlying heart disease or ejection fraction. PVC rate showed a modest negative correlation with variability (r = 0.3). Thus, variability is substantially greater at 1 week, the usual time for clinical assessment of antiarrhythmic drug efficacy, than at 1 day (p less than 0.01). Suppression of more than 85% of total PVCs and more than 95% of repetitive beats appears to be necessary after 1-2 weeks to be confident of a true drug effect. Even greater variability is observed after 1 month and up to 1 year so that reductions of up to 95% in total PVCs and 98% in repetitive beats may represent spontaneous change.(ABSTRACT TRUNCATED AT 400 WORDS)
Increased preferential absorption in human atherosclerotic plaque with oral beta carotene. Implications for laser endarterectomy.
Authors: Prince M R , LaMuraglia G M , MacNichol E F
Published: June 2011

Patients undergoing carotid endarterectomy were pretreated with low-dose, oral beta carotene to determine whether the carotenoid content of plaque could be increased in vivo. Beta carotene-treated patients had a 50-fold increase in their plaque beta carotene level from 0.066 to 3.3 micrograms beta carotene/g plaque. Microscopy and microspectrophotometry demonstrated that plaque from beta carotene-treated patients had higher carotenoid levels and higher absorption (450-500 nm) compared with control specimens, but normal media was unaffected. This demonstration of increased preferential absorption by plaque suggests that selective ablation of atherosclerotic plaque may be enhanced by pretreating patients with oral beta carotene.
Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs.
Authors: Ditchey R V , Lindenfeld J
Published: June 2011

Although large doses of epinephrine increase coronary perfusion pressure and flow during cardiopulmonary resuscitation, epinephrine also increases myocardial oxygen consumption during ventricular fibrillation. To test the hypothesis that epinephrine improves the balance between myocardial oxygen supply and demand during cardiopulmonary resuscitation, myocardial adenosine 5'-triphosphate (ATP) and lactate concentrations were measured before and immediately after 10 minutes of cardiopulmonary resuscitation in 10 control dogs and 10 dogs given intravenous epinephrine (1-mg bolus followed by 0.2 mg/min). Left ventricular myocardial blood flow during cardiopulmonary resuscitation was measured with radioactive microspheres and was significantly higher in the epinephrine group (48 +/- 11 vs. 21 +/- 4 ml/min/100 g, p less than 0.05). However, myocardial lactate concentration increased significantly (p less than 0.01) after cardiopulmonary resuscitation in both groups and tended to increase more in epinephrine-treated animals. Myocardial ATP concentration decreased significantly (p less than 0.05) and by comparable amounts in the two groups. These findings suggest that large doses of epinephrine may fail to improve the balance between myocardial oxygen supply and demand during cardiopulmonary resuscitation, even when they result in a substantial increase in coronary blood flow.
Preferential venoconstriction by cyclooxygenase inhibition in vivo without attenuation of nitroglycerin venodilation.
Authors: Münzel T , Stewart D J , Holtz J , Bassenge E
Published: June 2011

Because prostacyclin is a rather potent venodilator in vivo, we analyzed the effect of cyclooxygenase inhibition on venous tone in 14 anesthetized dogs during ganglionic and beta-adrenergic blockade and atraumatic conditions. Effective vascular stiffness (a reciprocal of effective vascular compliance) as a variable of integrated venous tone was 0.30 +/- 0.01 mm Hg.kg/ml (n = 35) and was augmented up to twofold by diclofenac (1, 3, and 10 mg/kg i.v.), ibuprofen (6 and 60 mg/kg), or indomethacin (5 mg/kg) parallel to augmentations in central venous pressure, while the rise in arterial pressure was less than half of the increase induced by equivenoconstrictor dosages of norepinephrine. After preconstriction by indomethacin or diclofenac, nitroglycerin (1.5 micrograms/kg/min) lowered effective vascular stiffness (by 24 +/- 2% or 23 +/- 5%, respectively), similarly as during preconstriction by norepinephrine (by 24 +/- 4%). Long-term cyclooxygenase inhibition (diclofenac 2 x 1 mg/kg/day for 4 days) did not modify arterial pressure, heart rate, or hematocrit levels in conscious dogs at rest, but it lowered plasma volume to 52.5 +/- 1.9 ml/kg (sham treatment: 59.1 +/- 1.6 ml/kg, p less than 0.05, n = 4). In conclusion, venoconstriction by clinical dosages of cyclooxygenase inhibitors does not interfere with the venodilator action of nitroglycerin and is compensated chronically by adjustments of plasma volume.
Demonstration of an imbalance between coronary perfusion and excessive load as a mechanism of ischemia during stress in patients with aortic stenosis.
Authors: Smucker M L , Tedesco C L , Manning S B , Owen R M , Feldman M D
Published: June 2011

Patients with aortic stenosis are susceptible to myocardial ischemia during hemodynamic stress, which may be caused by two mechanisms. First, vascular abnormalities inherent in myocardial hypertrophy may impair coronary vasodilation, limiting the ability to increase coronary blood flow to meet increased metabolic demands. Second, aortic stenosis itself may cause an imbalance between oxygen supply and demand during hemodynamic stress by decreasing aortic pressure (decreasing coronary perfusion or oxygen supply) and increasing left ventricular pressure (increasing oxygen demand). By decreasing aortic valve gradient without immediately altering ventricular hypertrophy, aortic balloon valvuloplasty offers the opportunity to distinguish these mechanisms. We hypothesized that aortic valvuloplasty would improve the balance between myocardial oxygen supply and demand, especially during isoproterenol infusion. Nine patients undergoing aortic balloon valvuloplasty were assessed at baseline and during isoproterenol infusion (5 +/- 2 micrograms/min, mean +/- SD) before and after valvuloplasty. Valvuloplasty increased myocardial oxygen supply. After valvuloplasty, isoproterenol decreased diastolic pressure time index (DPTI) less and increased coronary sinus blood flow more than before valvuloplasty (-630 +/- 367 vs. -292 +/- 224 mm Hg.sec/min, p = 0.02 and 53 +/- 137 vs. 179 +/- 145 ml/min, p = 0.001, respectively). Valvuloplasty also decreased oxygen demand, decreasing systolic pressure time index (SPTI) from 4,135 +/- 511 to 3,021 +/- 492 mm Hg.sec/min (p = 0.0002). Valvuloplasty improved the balance between myocardial oxygen supply and demand, increasing baseline DPTI:SPTI, decreasing aortocoronary sinus oxygen content difference (0.51 +/- 0.15 to 0.68 +/- 0.14, p = 0.005 and 96 +/- 14 to 78 +/- 15 ml O2/l, p = 0.002, respectively), and decreasing myocardial lactate production during isoproterenol infusion (mean lactate extraction fraction, -0.26 +/- 0.40 to 0.14 +/- 0.17; p = 0.01). We conclude that aortic valvuloplasty improves the balance between myocardial oxygen supply and demand during hemodynamic stress induced by isoproterenol infusion. We speculate that the clinical improvement, which often occurs in these patients after valvuloplasty despite persistence of hemodynamically "critical" aortic stenosis, is in part attributable to immediate improvement in the myocardial oxygen supply:demand ratio.
Hemodynamics in humans during conventional and experimental methods of cardiopulmonary resuscitation.
Authors: Swenson R D , Weaver W D , Niskanen R A , Martin J , Dahlberg S
Published: June 2011

High-fidelity hemodynamic recordings of aortic and right atrial pressures and the coronary perfusion gradient (the difference between aortic and atrial pressure) were made in nine patients during cardiopulmonary resuscitation (CPR). Findings during conventional manual CPR were compared with those during high-impulse CPR (rate, 120 cycles/min with a shorter compression:relaxation ratio) as well as during pneumatic vest CPR with and without simultaneous ventilation and abdominal binding. Aortic peak pressure during conventional CPR averaged 61 +/- 29 mm Hg but varied widely (range, 39-126 mm Hg) among patients. Although the magnitude of improvement was modest, the high-impulse method was the only technique tested that significantly elevated both aortic peak pressure and the coronary perfusion gradient during cardiac arrest. During conventional CPR, aortic pressure rose from 61 +/- 29 to 80 +/- 39 mm Hg during high-impulse CPR, and the gradient rose from 9 +/- 11 to 14 +/- 15 mm Hg, respectively; p less than 0.01. The pneumatic vest method significantly improved peak aortic pressure but not the coronary perfusion gradient. Simultaneous ventilation and chest compression created high end-expiratory pressure and lowered the coronary perfusion gradient. Abdominal binding had no significant hemodynamic effects. This evaluation of experimental resuscitation methods in humans shows that the high-impulse chest compression method augments aortic pressure over levels achieved during conventional CPR methods; however, the improvement in pressure is modest and may not be clinically important. Simultaneous ventilation as well as abdominal binding during CPR were associated with no benefit; in fact, simultaneous ventilation appears to adversely affect cardiac perfusion and, therefore, should not be used during clinical resuscitation.
Importance of adequate heparin dosage in arterial angioplasty in a porcine model.
Authors: Heras M , Chesebro J H , Penny W J , Bailey K R , Lam J Y , Holmes D R , Reeder G S , Badimon L , Fuster V
Published: June 2011

Acute occlusion after a successful angioplasty is a severe complication that has been reported in 2-12% of patients. Therefore, to determine whether there was a relation between the dosage of heparin and the presence of mural thrombosis, we studied in a pig model the relation between the dosage of heparin and acute platelet-thrombus deposition on the site of arterial injury. We retrospectively analyzed the effect of three heparin regimens on platelet deposition in 32 normal pigs (mean weight, 32.7 kg) that underwent bilateral carotid angioplasty and were sacrificed 90 +/- 26 minutes later. Pigs in protocol 1 (n = 7) received an intravenous bolus injection of 4,000 units heparin 10 minutes before angioplasty. Pigs in protocol 2 (n = 11) received two bolus injections of 4,000 units heparin 40 minutes apart; the angioplasty was performed immediately after the second bolus. Pigs in protocol 3 (n = 14) had an initial 4,000-unit bolus injection of heparin followed immediately by an infusion of 4,000 units/hr; angioplasty was performed 20 minutes after starting the infusion. 111In-labeled platelet deposition on deeply injured (torn into the media) arterial segments were 86.3 +/- 68, 56.2 +/- 56.9, and 37.7 +/- 37.7 X 10(6)/cm2 for protocols 1, 2, and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolic response to prolonged reduction of myocardial blood flow distal to a severe coronary artery stenosis.
Authors: Fedele F A , Gewirtz H , Capone R J , Sharaf B , Most A S
Published: June 2011

Limited data are available concerning the effects of mild-to-moderate, sustained reductions of coronary blood flow on myocardial aerobic metabolism. This study tested the hypothesis that a sustained flow reduction distal to a severe coronary artery stenosis may be well tolerated (after the initial insult is passed) because of gradual improvement in the balance between myocardial oxygen supply and demand. Studies were performed in eight sedated, closed-chest domestic swine that were instrumented with an artificial coronary arterial stenosis (80% diameter reduction). Hemodynamics, regional myocardial blood flow and oxygen, lactate, acid, and base metabolism were measured before stenosis and at 5, 20, 60, 120, and 180 minutes after stenosis insertion. Regional myocardial function (ultrasonic length sensors) was measured serially during 2 hours in three additional swine. After stenosis placement, endocardial and transmural flows declined (p less than 0.05) compared with flows before stenosis (from 1.54 +/- 0.37 to 0.73 +/- 0.24 ml/min/g [mean +/- SD] and from 1.44 +/- 0.31 to 1.19 +/- 0.25 ml/min/g, respectively). Thereafter, flows remained unchanged for the duration of the study. Similarly, prestenosis heart rate (135 +/- 7 beats/min), aortic mean pressure (113 +/- 17 mm Hg), and tension time index (27.1 +/- 3.6 mm Hg.sec) remained constant for the duration of the study. In contrast, regional coronary venous pH declined (p less than 0.05) compared with prestenosis levels (7.35 +/- 0.02) 5 minutes after stenosis (7.28 +/- 0.04), but it returned to prestenosis levels during the next hour. Regional coronary venous PCO2 exhibited a similar pattern (i.e., acute increase during poststenosis with gradual return to prestenosis levels).(ABSTRACT TRUNCATED AT 250 WORDS)
111In-labeled platelet scintigraphy and two-dimensional echocardiography for detection of left atrial appendage thrombi. Studies in a new canine model.
Authors: Vandenberg B F , Seabold J E , Conrad G R , Kieso R , Johnson J , Fox-Eastham K , Ponto J , Bruch P , Kerber R E
Published: June 2011

111In-labeled platelet scintigraphy and two-dimensional echocardiography were performed in 40 dogs to determine the ability of the two techniques to detect left atrial appendage thrombi. Thrombi were induced in 33 dogs that were classified into two groups, "acute" or "chronic," according to the time of labeled-platelet injection after thrombus induction. In the acute group (17 dogs), platelets were injected 24 hours after thrombus induction. In the chronic group (16 dogs), platelets were injected 4-8 days after thrombus induction. "Sham" thoracotomies were performed on seven additional control dogs who did not receive thrombin injections. Analog and blood pool-corrected 111In-labeled platelet scintigraphy images were obtained 4-72 hours later. Closed-chest two-dimensional echocardiography was performed before thoracotomy and repeated at the time of scintigraphy. The location and size of each thrombus were verified at autopsy. Two-dimensional echocardiography detected three of 17 acute (mean volume, 1.2 +/- 1.0 cc) and three of 10 chronic (mean volume, 0.4 +/- 0.3 cc; p less than 0.025) left atrial appendage thrombi. 111In-labeled platelet scintigraphy detected all 17 acute thrombi but only two of 10 chronic thrombi. The measured radioactivity levels of the excised thrombi were 1,949 +/- 1,665 cpm/clot/dose in group 1 and 228 +/- 213 cpm/clot/dose in group 2 (p less than 0.005). In this model, 111In-labeled platelet scintigraphy was able to detect acute left atrial appendage thrombi that could not be identified by two-dimensional echocardiography. Both techniques showed poor sensitivity for detection of chronic thrombi. The decline in sensitivity of 111In-labeled platelet scintigraphy for detection of older thrombi is probably due to diminished labeled-platelet incorporation.
Catheter ablation of accessory pathways with a direct approach. Results in 35 patients.
Authors: Warin J F , Haissaguerre M , Lemetayer P , Guillem J P , Blanchot P
Published: June 2011

Thirty-five consecutive patients with an overt accessory pathway, all but two suffering from arrhythmia (atrial fibrillation, reciprocating tachycardia, or both), underwent attempted transcatheter ablation (fulguration) of their accessory pathway. Thirty-three patients had been treated with a mean of 2.3 +/- 1.4 antiarrhythmic drugs. A standard bipolar catheter was positioned on the internal surface of the right or left atrioventricular anulus with 1) a subclavian approach of the right cardiac cavities in 29 patients with right-sided accessory pathway (n = 27) or left posteroseptal accessory pathway (n = 2), 2) a patent foramen ovale in five patients (two with a left posterolateral accessory pathway and three with a left parietal accessory pathway), and a transseptal catheterism (one patient with a left parietal accessory pathway). Cathodic shocks (mean, 4.3 shocks/patient) with a mean cumulative energy of 690 J enabled the ablation (disappearance of both anterograde and retrograde conduction) of the accessory pathway in 32 patients with a follow-up ranging from 1 to 32 months (mean, 10 +/- 8 months). Two of the remaining three accessory pathways were impaired: one pathway became intermittent, the anterograde effective refractory period of the second pathway increased from 260 to 410 msec, and the third pathway was slightly impaired. This latter patient is the only one who still requires therapy, with a single antiarrhythmic drug. All others are free of arrhythmias and require no therapy. Not using coronary sinus catheterism inclusive of its os has led to only a few, benign side effects. Only one third-degree atrioventricular block occurred in a posteroseptal accessory pathway ablation. Three cases of patients with incessant reciprocating tachycardia involving a further successful ablation occurred at the beginning of our experience. The best area for ablation is, in our opinion, the recording site for the Kent-bundle activity (18 of 35 patients), but a meticulous mapping of the atrioventricular anulus during orthodromic reciprocating tachycardia makes ablation possible when the shortest ventriculoatrial time (V-A') can be recorded with reliability (mean, 85 +/- 18 msec). Such a procedure is an alternative to surgical ablation regardless of the location of the accessory pathway--not only posteroseptally.
Baroreflex sensitivity, clinical correlates, and cardiovascular mortality among patients with a first myocardial infarction. A prospective study.
Authors: La Rovere M T , Specchia G , Mortara A , Schwartz P J
Published: June 2011

Experimental studies have shown that among dogs with a healed myocardial infarction, depressed baroreflex sensitivity (BRS) identifies a subgroup at higher risk for sudden death. We have examined the relation among BRS, several clinical cardiovascular variables, and subsequent mortality in 78 patients below the age of 65 years who have had a first myocardial infarction. BRS was assessed by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. A reduced BRS primarily reflects an impairment in the vagal efferent component of the baroreceptor reflexes. The BRS of the entire population was 7.8 +/- 4.9 msec/mm Hg. BRS was lower among patients with an inferior myocardial infarction (6.1 +/- 3.3 vs. 8.9 +/- 5.8 msec/mm Hg, p = 0.03), with a three- versus a one-vessel disease (4.8 +/- 2.7 vs. 7.1 +/- 3.1 msec/mm Hg, p = 0.04), and with episodes of ventricular tachycardia (5.1 +/- 3.0 vs. 8.3 +/- 5.1, p = 0.03). There was no correlation between BRS and left ventricular ejection fraction or with mean pulmonary capillary wedge pressure at peak exercise, but a correlation (r = 0.35, p less than 0.001) was present with exercise tolerance. During the 24 months mean follow-up period, there were six cardiovascular deaths (7.6%), and four were sudden.(ABSTRACT TRUNCATED AT 250 WORDS)
Color Doppler evaluation of valvular regurgitation in normal subjects.
Authors: Yoshida K , Yoshikawa J , Shakudo M , Akasaka T , Jyo Y , Takao S , Shiratori K , Koizumi K , Okumachi F , Kato H
Published: June 2011

To determine prospectively the prevalence of mitral, aortic, tricuspid, and pulmonary regurgitation in normal persons, 211 consecutive, apparently healthy volunteers were examined with a color Doppler flow imaging system. The subjects were divided into five age groups (group 1, 6-9 years old; group 2, 10-19 years old, group 3, 20-29 years old, group 4, 30-39 years old, and group 5, 40-49 years old). The prevalence rate of mitral regurgitation in the normal subjects was 38-45% in each group. The mitral regurgitant jets came from the posteromedial commissure in all but two subjects. No aortic regurgitant flow signals were detected in the normal subjects. Tricuspid regurgitation was detected in 15-77% in each group, and pulmonary regurgitation was detected in 28-88%. Regarding the tricuspid and pulmonic valves, the prevalence rate of regurgitation is age dependent (p less than 0.01) and tends toward the lower rate in groups over the age of 30 years. The tricuspid and pulmonary regurgitant jets came from the center of the coaptation of each valve. The area of the regurgitant jet signals in normal persons was significantly smaller (p less than 0.001) than that obtained from patients with organic valve disease. Our study shows that in a large proportion of normal persons under the age of 50 years color Doppler echocardiography permits recording of regurgitant signals behind all valves except the aortic. In conclusion, one should be aware of the existence and characteristics of regurgitation in normal persons when evaluating valvular regurgitation by Doppler techniques.
Prognostic importance of myocardial ischemia detected by ambulatory monitoring in patients with stable coronary artery disease.
Authors: Rocco M B , Nabel E G , Campbell S , Goldman L , Barry J , Mead K , Selwyn A P
Published: June 2011

To assess the relations of electrocardiographic measures of ischemia with the development of adverse coronary events, 86 patients with stable coronary artery disease and positive exercise tests for myocardial ischemia underwent ambulatory monitoring of the electrocardiogram. Monitoring was performed after withdrawal of antianginal medications, and prospective follow-up was obtained on routine medical care as prescribed by physicians who were unaware of monitor results. Forty-nine patients (57%) had a total of 426 episodes of ST segment depression; only 60 episodes (14%) were associated with symptoms of angina or an equivalent. During a mean follow-up of 12.5 +/- 7.5 months, there were two cardiac deaths, four myocardial infarctions, four hospitalizations for unstable angina, and 11 revascularization procedures required for new or worsening symptoms in 15 patients. All but one of these events (a hospitalization for unstable angina) occurred in the group of patients with ST segment depression on monitoring (p = 0.003). In multivariate analysis controlling for age, sex, and clinical descriptions of angina, the presence of ischemia on ambulatory monitoring was a significant predictor of outcome, while exercise test characteristics were not. Therefore, ischemia detected by ambulatory monitoring was common in patients with stable symptoms of coronary artery disease, and its presence identified a high-risk group for the development of subsequent unfavorable outcomes while on routine medical therapies.
Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension.
Authors: Asmar R G , Pannier B , Santoni J P , Laurent S , London G M , Levy B I , Safar M E
Published: June 2011

Blood pressure, forearm arterial hemodynamics (with a pulsed Doppler flowmeter), and echocardiographic parameters were studied in 16 patients with sustained essential hypertension before and 3 months after administration of the converting enzyme inhibitor perindopril. In a single-blind study versus placebo, it was shown that perindopril significantly reduced blood pressure (p less than 0.01), whereas there was an increase in brachial blood flow (p less than 0.01) because of a simultaneous increase in blood flow velocity (p less than 0.01) and arterial diameter (p less than 0.01). During a 5-minute period of wrist occlusion, blood flow velocity was reduced to a greater extent with perindopril than with placebo (p less than 0.001), whereas corresponding reductions in arterial diameter were equivalent, indicating that the increase in diameter after perindopril could not be explained simply on the basis of flow-dependent dilatation. During active treatment, brachial artery compliance increased (p less than 0.01) and pulse wave velocity decreased (p less than 0.01), whereas there was no change in the tangential tension of the arterial wall, defined as the product of mean arterial pressure and arterial diameter. Four weeks after treatment was stopped, blood pressure and forearm arterial hemodynamics returned toward baseline values. Cardiac mass was significantly decreased after perindopril (p less than 0.01) and remained decreased 4 weeks after cessation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Contribution of pulmonary receptors to the heart rate response to acute hypoxemia in rabbits.
Authors: Kato H , Menon A S , Chen F J , Slutsky A S
Published: June 2011

We studied the effect of pulmonary afferent activity on the heart rate response to a progressive, isocapnic decrease in oxygen saturation (SaO2) in anesthetized rabbits. To abolish the effect of rapidly adapting receptors, we used inhaled bupivacaine aerosol, and to abolish the effect of slowly adapting stretch receptor activity, we used sulfur dioxide insufflation. The heart rate (HR) response (delta HR/delta SaO2) under control conditions was 0.39 +/- 1.29 beats/min/% (mean +/- SD, n = 11; values greater than 0 indicate a tachycardiac response to hypoxemia). After sulfur dioxide insufflation, all nine rabbits had a bradycardiac response (-2.02 +/- 1.13 beats/min/%), which was significantly less than control (p less than 0.0001). After bupivacaine inhalation, the heart rate response (0.27 +/- 1.04 beats/min/%) was unchanged from control. There were no significant differences in the percent increase of minute ventilation during hypoxemia in all runs. Our results indicate that in rabbits the receptors responsible for the increase in heart rate during progressive hypoxemia are the slowly adapting receptors.
Cardiovascular and renal hemodynamic effects of intravenous infusions of the selective DA1 agonist, fenoldopam, used alone or in combination with dopamine and dobutamine.
Authors: Lass N A , Glock D , Goldberg L I
Published: June 2011

Fenoldopam (0.1 and 0.2 microgram/kg/min i.v.) was administered to pentobarbital-anesthetized dogs alone and combined with dopamine (DA) and dobutamine. Renal blood flow, heart rate, and mean arterial pressure were measured. Both dosages of fenoldopam increased renal blood flow without altering blood pressure, similar to the effects of DA (1 and 2 micrograms/kg/min). Administration of fenoldopam with only DA (1 microgram/kg/min) produced further increase in renal blood flow. After administration of phenoxybenzamine (15 mg/kg i.v.), DA produced significant increments in renal blood flow and reductions in renal vascular resistance when compared with experiments without phenoxybenzamine, suggesting even low dosages of DA exert alpha-adrenoceptor agonist activity. Dobutamine (2 and 4 micrograms/kg/min) increased renal blood flow about 37% of that produced by DA. Fenoldopam added to dobutamine produced similar increments in renal blood flow as DA. Fenoldopam did not affect the increase in cardiac contractile force produced by DA and dobutamine. Thus, fenoldopam alone or in combination with DA had no advantage over 2 and 4 micrograms/kg/min DA to further increase renal blood flow. In contrast, fenoldopam with dobutamine produced greater increments in cardiac contractile force than DA and equivalent increases in renal blood flow as DA.
Reduced lymphocyte stimulatory guanine nucleotide regulatory protein and beta-adrenergic receptors in congestive heart failure and reversal with angiotensin converting enzyme inhibitor therapy.
Authors: Horn E M , Corwin S J , Steinberg S F , Chow Y K , Neuberg G W , Cannon P J , Powers E R , Bilezikian J P
Published: June 2011

Adrenergic hyporesponsiveness in congestive heart failure has been understood previously in terms of a reduction in beta-adrenergic receptors. We have examined another hypothesis, one that states the stimulatory guanine nucleotide regulatory protein (Gs) that couples the beta-adrenergic receptor to adenylate cyclase activity is also decreased in congestive heart failure. In addition to the 40% decrease in lymphocyte beta-adrenergic receptors in patients in congestive heart failure (5.9 +/- 0.7 vs. 9.7 +/- 1.4 fmol/mg, p less than 0.05), we found an 80% decrease in levels of Gs compared with age- and sex-matched healthy control subjects (72.5 +/- 19 vs. 376 +/- 73 fmol/mg, p less than 0.05). Myocardial Gs levels correlated significantly with lymphocyte Gs levels. We also assessed the hypothesis that reductions in beta-adrenergic receptors and in Gs are reversible after successful therapy with angiotensin converting enzyme inhibitors. Treatment with either captopril or lisinopril was associated with clinical improvement, an increase in beta-adrenergic receptor density (from 5.5 +/- 0.7 to 8.7 +/- 1.5 fmol/mg), and a twofold increase in Gs levels (p less than 0.05). Thus, the data are compatible with Gs serving as an adaptable and reversible regulator of the adrenergic response in congestive heart failure. In view of the fact that Gs is a transducing element common to all hormones that stimulate cyclic adenosine 5'-monophosphate production, the observations could extend to other abnormal neurohumoral mechanisms in congestive heart failure.
Systemic and regional hemodynamic and humoral effects of nitrendipine in essential hypertension.
Authors: Grossman E , Oren S , Garavaglia G E , Messerli F H , Frohlich E D
Published: June 2011

The hemodynamic effects of 3 months of nitrendipine therapy were evaluated in 14 patients with mild to moderate essential hypertension. Nitrendipine reduced systolic and diastolic pressures from 145 +/- 4/95 +/- 3 to 119 +/- 3/78 +/- 2 mm Hg, respectively, (p less than 0.001) through a fall in total peripheral resistance index (46 +/- 4 to 34 +/- 3 units/m2, p less than 0.001) without associated reflex cardiac stimulation. This antihypertensive effect was related directly to the height of pretreatment arterial pressure (r = -0.67, p = 0.006) but not to age or pretreatment plasma renin activity. Renal and forearm blood flow increased, vascular resistance decreased, and glomerular filtration rate remained stable. In addition, nitrendipine reduced left ventricular mass index (133 +/- 7 to 116 +/- 5 g/m2, p = 0.003) and wall thickness, changes that were accompanied by improvement in diastolic as well as systolic (ejection fraction and fractional fiber shortening rate) left ventricular functions. Intravascular volume did not expand with reduction in pressure. This study provides new information concerning the long-term hemodynamic effects and associated echocardiographic changes with nitrendipine. It also provides the first regional hemodynamic data in essential hypertensive patients detailing forearm and splanchnic changes and renal blood flow increase during prolonged treatment.
Amiloride. Antiarrhythmic and electrophysiological activity in the dog.
Authors: Duff H J , Lester W M , Rahmberg M
Published: June 2011

Amiloride, a widely used diuretic, has multiple pharmacological actions, including inhibition of the sodium-hydronium ion and the sodium-calcium exchanger in heart. In terms of cardiac electrophysiology, amiloride prolongs action potential duration without alteration in upstroke velocity of phase 0 in Purkinje fibers. The antiarrhythmic efficacy of amiloride was assessed in a model of inducible sustained ventricular tachyarrhythmias in 16 dogs late after 2-hour occlusion-reperfusion of the left anterior descending coronary artery. Sixteen animals were studied: Four were randomly assigned to placebo, and 12 were assigned to amiloride treatment. Prolonged loading and maintenance infusions were designed to produce amiloride concentrations over the range achievable in humans. Animals were chronically instrumented to allow electrophysiological measures of conduction and refractoriness in the left ventricular infarct and border zones. Of the 12 animals treated with amiloride, six responded with inability to induce ventricular tachyarrhythmias, whereas of the four animals treated with placebo, none responded. The mean infarct size of the six animals responding to amiloride (12 +/- 5%) was significantly less than that of the six animals not responding to amiloride (20 +/- 8%). Overall, the only electrophysiological effect of amiloride observed in this study was prolongation of border zone ventricular refractoriness. This electrophysiological effect was accentuated in animals responding to amiloride. In addition, when animals were subdivided into responders, partial responders, or nonresponders, the border zone repolarization time was prolonged in responders and partial responders, whereas this measure shortened in nonresponding animals. Amiloride has antiarrhythmic activity in the suppression of sustained ventricular tachyarrhythmias in this postinfarction model.
Role of beta 1-receptors and vagal tone in cardiac inotropic and chronotropic responses to a beta 2-agonist in humans.
Authors: Levine M A , Leenen F H
Published: June 2011

To assess the contribution of cardiac beta 2-receptors in the cardiac inotropic and chronotropic responses to a beta 2 agonist, terbutaline was infused (0.2 and 0.4 micrograms/kg/min), alone or after pretreatment with either oral atenolol 50 mg or atropine 0.04 mg/kg i.v. or both in six healthy subjects with a multiple crossover design. Terbutaline 0.2 micrograms/kg/min increased heart rate by 15 +/- 2 beats/min, and this response doubled (to 29 +/- 3 beats/min) when the terbutaline infusion followed atropine pretreatment, whereas atenolol pretreatment had no significant effect. Heart rate increased by 44 +/- 2 beats/min in response to terbutaline 0.4 micrograms/kg/min. This response was not affected by atropine. Pretreatment with atenolol diminished the chronotropic response to the higher dose of terbutaline to 27 +/- 4 beats/min. The inotropic response (i.e., changes in pressure: volume ratio) to terbutaline 0.2 micrograms/kg/min was potentiated by atropine (from 1.6 +/- 0.3 to 3.4 +/- 0.8 mm Hg/ml), whereas atenolol pretreatment had no effect. At the higher dose of terbutaline, atropine pretreatment had no additional effect, whereas atenolol decreased the rise in pressure: volume ratio from 6.0 +/- 1.4 to 2.6 +/- 1.0 mm Hg/ml. The results with atenolol pretreatment indicate that cardiac beta 1 responses are associated with the higher dose of terbutaline, either through direct beta 1 stimulation or indirectly from presynaptic beta 2 activity. The atropine data show that vagal tone actually increased during the terbutaline infusions, blunting the cardiac effects. The results of the present study support the existence of functional chronotropic, as well as inotropic, beta 2 receptors in the healthy human heart.
Time course of thrombolysis induced by intravenous bolus or infusion of tissue plasminogen activator in a rabbit jugular vein thrombosis model.
Authors: Clozel J P , Tschopp T , Luedin E , Holvoet P
Published: June 2011

Tissue plasminogen activator is a thrombolytic agent that has been shown to be efficient in patients with myocardial infarction or pulmonary embolus. However, little is known about the time course and the dose dependency of its thrombolytic effect. The goal of our study was to investigate the time course of the thrombolysis induced by increasing doses of tissue plasminogen activator (t-PA) given either as a continuous infusion (0.0625-1 mg/kg) or as a bolus (0.05-0.4 mg/kg). For this purpose, we modified a previously described rabbit jugular vein thrombosis model by using an external gamma counter to follow continuously the thrombolysis. After administration of t-PA as either an infusion or a bolus, the rate and the extent of thrombolysis were dose dependent. The thrombus size decreased regularly following an exponential curve and reached a lower asymptote implicating an unlysable thrombus. As expected, after bolus injection, t-PA was rapidly inhibited resulting in a duration of action of approximately 15 minutes; this was independent of the dose. Surprisingly, during continuous infusion of t-PA for as long as 4 hours, the duration of action was limited to about 2 hours, although the plasma t-PA activity levels remained stable. Although the rate of inhibition was lower and thus the duration of action was longer during continuous infusion of t-PA than after a bolus injection, the extent of thrombolysis was similar when the same dose of t-PA was given as either a bolus or an infusion. These findings could be attributed to the higher initial rate of thrombolysis observed after a bolus injection.(ABSTRACT TRUNCATED AT 250 WORDS)