bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function.
Authors: Bonow R O , Picone A L , McIntosh C L , Jones M , Rosing D R , Maron B J , Lakatos E , Clark R E , Epstein S E
Published: June 2011

Recent studies suggest that preoperative left ventricular function may no longer be an important determinant of survival or functional results after operation for aortic regurgitation because of improved operative techniques. To assess the effect of left ventricular function on prognosis in the current surgical era, we performed echocardiographic and radionuclide angiographic studies in 80 consecutive patients undergoing valve replacement from 1976 to 1983. No patient had associated coronary artery disease. For all patients, 5 year survival was 83 +/- 5%, significantly better than the 62 +/- 9% 5 year survival in our patients operated on from 1972 to 1976. Preoperative resting left ventricular ejection fraction (p less than .001), fractional shortening (p less than .001), and end-systolic dimension (p less than .01) were the most significant predictors of survival (univariate life-table analysis). Five year survival was 63 +/- 12% in patients with subnormal ejection fraction (n = 50) compared with 96 +/- 3% in those with normal ejection fraction (n = 30). Patients with subnormal left ventricular ejection fraction and poor exercise tolerance or prolonged duration of left ventricular dysfunction (greater than 18 months) comprised the high-risk subgroup (5 year survival 52 +/- 11%). Patients in this subgroup also had persistent left ventricular dysfunction after operation, with greater left ventricular end-diastolic dimensions and reduced ejection fraction (both p less than .001) compared with patients with normal preoperative left ventricular ejection fraction or a brief duration of left ventricular dysfunction (less than 14 months). Cold hyperkalemic cardioplegia was used for myocardial preservation in 46 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Regional wave travel and reflections along the human aorta: a study with six simultaneous micromanometric pressures.
Authors: Latham R D , Westerhof N , Sipkema P , Rubal B J , Reuderink P , Murgo J P
Published: June 2011

The human aorta and its terminal branches were investigated in normal subjects during elective cardiac catheterization to evaluate regional wave travel and arterial wave reflections. A specially designed catheter with six micromanometers equally spaced at 10 cm intervals was positioned with the tip sensor in the distal external iliac artery and the proximal sensor in the aortic arch. Simultaneous pressures were obtained and analyzed for foot-to-foot wave velocity, and Fourier analysis was used to derive apparent phase velocity. These quantities were assessed during control (n = 9), during Valsalva (n = 8) and Müller (n = 4) maneuvers, and during femoral artery occlusion by bilateral manual compression (n = 8). During control, regional cross-sectional areas, determined from aortography, and regional foot-to-foot pulse wave velocities were used to calculate the local reflection coefficient in the proximal descending aorta (gamma = 0.05), at the junction of the renal arteries (gamma = 0.43), and at the terminal aortic bifurcation (gamma = 0.13). To test the hypothesis that significant reflections originate in the aorta, at the level of the renal arteries, aortograms were used to design a latex tube model with geometric properties similar to the descending aorta. Velocities and reflection characteristics in the model and in vivo were compared. Inspection of thoracic aortic pressures under control conditions revealed a reflected wave originating from the region of the aorta at the level of the renal arterial branches while abdominal pressures exhibited reflection from a site peripheral to the terminal aortic bifurcation. In the low frequency range, apparent phase velocity was found to be higher proximal to the renal arteries as compared with at the distal sites. In addition, the minimum value occurred at a higher frequency in the lower thoracic aorta than at more distal sites. The effects of reflection on apparent wave velocity in the tube model were consistent with data obtained in vivo. The Valsalva maneuver diminished the reflection from the aortic region of the renal arteries, thus allowing the distal reflected wave to become more evident on the thoracic pressure waveforms. Bilateral femoral artery occlusion usually enhanced the distal reflection and the Müller maneuver usually resulted in small increases in reflections. In conclusion, the geometric and elastic nonuniformity of the aorta results in two major sites of arterial wave reflection that influence the aortic pressure waveforms in man.(ABSTRACT TRUNCATED AT 400 WORDS)
Kinetics of electrophysiologic changes during oral loading of amiodarone and after withdrawal of amiodarone in the unsedated dog.
Authors: Tuna I C , Qi A C , Gornick C , Bolman R M , Benditt D G
Published: June 2011

We examined the temporal kinetics of onset and offset of the cardiac electrophysiologic effects of orally administered amiodarone in chronically instrumented, unsedated adult dogs (n = 8). Right atrial (RA), atrioventricular nodal (AVN), and right ventricular (RV) effective refractory period (ERP), and AVN functional refractory period (FRP), were determined daily for 21 days during amiodarone loading (24 mg/kg/day) and for 21 days after cessation of amiodarone. Left ventricular (LV) ERP was assessed in four of eight animals. Group mean RA-ERP peaked and plateaued early during amiodarone loading (time to reach one-half observed peak change [t1/2 onset] = 1.2 +/- 0.5 days) and rapidly returned toward baseline after cessation of drug (decay time to one-half peak value [t1/2 offset] = 2.0 +/- 1.7 days). Group mean RV-ERP rose in a linear manner throughout the loading period (t1/2 onset = 9.3 +/- 2.1 days) and remained elevated after cessation of drug (t1/2 offset greater than 21.0 days). Group mean AVN-ERP and FRP exhibited temporal kinetics intermediate between those of the RA-ERP and RV-ERP, both during amiodarone loading and after cessation of the drug. Group mean LV-ERP onset kinetics (assessed in a limited number of animals, n = 4) appeared to differ from RV-ERP onset kinetics (t1/2 onset = 2.5 +/- 2.5 days), whereas LV-ERP and RV-ERP offset kinetics appeared similar (t1/2 offset greater than 21 days). In summary, our findings demonstrate that during oral loading, the temporal sequence of onset of amiodarone-induced electrophysiologic effects is site dependent. Similarly, after cessation of amiodarone, the persistence of drug-induced electrophysiologic effects is both variable and site dependent.
Comparative accuracy of two-dimensional echocardiography and Doppler pressure half-time methods in assessing severity of mitral stenosis in patients with and without prior commissurotomy.
Authors: Smith M D , Handshoe R , Handshoe S , Kwan O L , DeMaria A N
Published: June 2011

This study was undertaken to compare the accuracies of the two-dimensional echocardiographic (2DE) and Doppler pressure half-time methods for the noninvasive estimation of cardiac catheterization measurements of mitral valve area in patients with pure mitral stenosis both with and without a previous commissurotomy. Data were retrospectively obtained from 74 consecutive patients who underwent cardiac catheterization within a 30 month period for evaluation of mitral stenosis, and who had two-dimensional echocardiograms performed before catheterization. Six patients (8.1%) had technically inadequate 2DE images and their data were excluded from analysis. Two of these patients had undergone commissurotomy, while the remaining four had not. Continuous-wave Doppler echocardiographic examinations were attempted in 45 patients and adequate measurements of pressure half-times were obtained in all patients studied. Mitral valve area by two-dimensional echocardiography was measured as the planimetered area along the inner border of the smallest mitral orifice visualized during short-axis scanning, while pressure half-time was calculated as the interval between the peak transmitral velocity and velocity/square root 2 as measured from the envelope of the Doppler spectral signal. Calculations from catheterization represented the minimal valve area at rest as derived from the Gorlin formula with the use of pressure gradients and thermodilution measurements of cardiac output. Thirty-seven of the patients had had a previous mitral commissurotomy a mean of 11.2 +/- 5.4 years before, while the remaining 37 patients were previously unoperated. Mean valve area as determined at catheterization for the total group of patients ranged from 0.37 to 2.30 cm2 (mean = 1.08 +/- 0.42 cm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Immediate and short-term hemodynamic effects of diltiazem in patients with hypertension.
Authors: Amodeo C , Kobrin I , Ventura H O , Messerli F H , Frohlich E D
Published: June 2011

The immediate effects of intravenous diltiazem effects and short-term (4 weeks) of the oral drug on systemic and regional hemodynamics, cardiac structure, and humoral responses were evaluated by previously reported methods in nine patients with mild-to-moderate essential hypertension and in one patient with primary aldosteronism. Diltiazem was first administered in three intravenous doses of 0.06, 0.06, and 0.12 mg/kg, respectively; patients were then treated for 4 weeks with daily doses ranging from 240 to 360 mg (average 300 mg). Intravenous diltiazem immediately reduced mean arterial pressure (from 115 +/- 3 to 96 +/- 3 mm Hg; p less than .01) through a fall in total peripheral resistance index (from 37 +/- 3 to 23 +/- 2 U/m2; p less than .01) that was associated with an increase in heart rate (from 66 +/- 2 to 77 +/- 3 beats/min; p less than .01) and cardiac index (from 3.3 +/- 0.3 to 4.3 +/- 0.4 liters/min/m2; p less than .01). These changes were not associated with changes in plasma levels of catecholamines or aldosterone or in plasma renin activity. After 4 weeks the significant decrease in mean arterial pressure persisted (104 +/- 3 mm Hg; p less than .01) and there were still no changes in the humoral substances or plasma volume. Renal blood flow index increased (from 368 +/- 52 to 462 +/- 57 ml/min/m2; p less than .01) and renal vascular resistance index decreased (from 0.37 +/- 0.06 to 0.26 +/- 0.04 U/m2; p less than .01), while splanchnic hemodynamics did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of the direct vasodilator effect of milrinone with an isolated limb preparation in patients with chronic congestive heart failure.
Authors: Cody R J , Müller F B , Kubo S H , Rutman H , Leonard D
Published: June 2011

We developed an isolated limb preparation to evaluate the direct vasoactive properties of cardioactive drugs on the forearm vasculature in patients with congestive heart failure. Using this model, we infused milrinone in subsystemic doses (1, 10, and 20 micrograms/min per 100 ml forearm volume [FAV] ) into the brachial artery of 13 patients with moderate-to-severe congestive heart failure. We monitored forearm hemodynamics, systemic hemodynamics, and milrinone plasma concentration from both the forearm venous effluent and pulmonary artery. This preparation enabled us to assess the direct forearm vascular response to milrinone. Compared with baseline forearm blood flow (2.46 +/- 1.37 ml/min/100 ml FAV), the three doses of milrinone resulted in increases in forearm blood flow to 2.66 +/- 1.43, 4.21 +/- 1.79, and 6.73 +/- 3.69 ml/min/100 ml FAV. This was associated with a reduction of forearm vascular resistance from the baseline value of 52 +/- 38 U to 47 +/- 36, 25 +/- 13, and 17 +/- 10 U. The p value for the difference in response of flow and resistance after the 10 and 20 micrograms doses vs that at baseline was .05. This forearm vasodilatation occurred without change in systemic hemodynamics or therapeutic milrinone plasma concentrations in the pulmonary artery. In five patients, we compared the response to intra-arterial milrinone with that of nitroprusside. At a dose of 10 micrograms/min/100 ml FAV, the response to nitroprusside (7.20 +/- 3.24 ml/min/100 ml FAV) was greater than that to milrinone (4.65 +/- 2.18 ml/min/100 ml FAV) (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Separation of the direct myocardial and vasodilator actions of milrinone administered by an intracoronary infusion technique.
Authors: Ludmer P L , Wright R F , Arnold J M , Ganz P , Braunwald E , Colucci W S
Published: June 2011

To determine the relative contributions of milrinone's positive inotropic and vasodilator actions in patients with severe congestive heart failure, the drug was administered by constant infusion directly into the left main coronary artery of 11 patients with New York Heart Association functional class III or IV heart failure. Intracoronary infusion of milrinone at rates up to 50 micrograms/min had no effect on mean arterial pressure or systemic vascular resistance but resulted in dose-related increases in peak positive dP/dt (+21%), stroke volume index (+18%), and stroke work index (+21%) and decreases in heart rate (-3%), mean right atrial pressure (-25%), and left ventricular end-diastolic pressure (-17%). In eight patients, intravenous administration (75 micrograms/kg) after the intracoronary infusion resulted in significant decreases in mean arterial pressure (-14%) and systemic vascular resistance (-40%), further increase in stroke volume index compared with intracoronary administration, and further decreases in mean right atrial and left ventricular end-diastolic pressures compared with intracoronary administration. These data indicate that milrinone exerts both positive inotropic and vasodilator actions that contribute significantly to the drug's overall hemodynamic effect.
Short- and long-term therapy with tocainide for malignant ventricular tachyarrhythmias.
Authors: Hohnloser S H , Lange H W , Raeder E A , Podrid P J , Lown B
Published: June 2011

Tocainide was administered to 228 patients referred for treatment of recurrent ventricular tachyarrhythmias that were refractory to therapy with conventional antiarrhythmic drugs. After baseline studies, 1200 to 2400 mg tocainide/day was given for 4 days. Tocainide was effective in 49% of 180 patients evaluated with monitoring and exercise testing and in 35% of 48 patients undergoing electrophysiologic testing. No clinical parameter predicted the response to tocainide, although there was a correlation with the effect of lidocaine. Tocainide was selected for long-term treatment in 73 patients who were followed for an average of 26.4 months (range 1 to 92 months). The incidence of sudden death was 4.3% per year and two patients had nonfatal recurrence of arrhythmia. It is concluded that tocainide is effective and well tolerated during long-term use if therapy is evaluated carefully and is individualized.
Enhancement by norepinephrine of automaticity in sheep cardiac Purkinje fibers exposed to hypoxic glucose-free Tyrode's solution: a role for alpha-adrenoceptors?
Authors: Mugelli A , Amerini S , Piazzesi G , Cerbai E , Giotti A
Published: June 2011

A period of drive in the presence of norepinephrine (NE) may be followed by the induction or acceleration of spontaneous activity. Experiments were carried out in sheep cardiac Purkinje fibers to determine whether the effects of NE on automaticity were modified during superfusion with hypoxic glucose-free Tyrode's solution and to assess the possible contribution of alpha-adrenergic influences on automaticity under these conditions. The following results were obtained: Low concentrations of NE (10(-7) and 3 X 10(-7)M) were able to induce automaticity after a period of drive in normal oxygenated (97% O2, 3% CO2) Tyrode's solution. Superfusion with hypoxic (97% N2, 3% CO2) glucose-free Tyrode's solution enhanced NE-induced automaticity. Practolol, in concentrations able to block the effects of NE in normal oxygenated solution, did not counteract the effects of NE in hypoxic glucose-free solution. Yohimbine, but not prazosin, antagonized the effects of NE in hypoxic glucose-free solution. At the same concentration, yohimbine did not affect transmembrane potentials or automaticity induced by isoproterenol. It is concluded that alpha-adrenergic responsiveness appears to be enhanced during superfusion in vitro with hypoxic glucose-free solution, and that alpha-adrenoceptors belonging to the alpha 2-subtype in sheep cardiac Purkinje fibers might influence abnormal automaticity, possibly through an effect on oscillatory potentials.
Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart.
Authors: Kléber A G , Janse M J , Wilms-Schopmann F J , Wilde A A , Coronel R
Published: June 2011

Conduction velocities along longitudinal (vL) and transverse (vT) fiber axes were determined in isolated porcine hearts from subepicardial activation patterns that were produced by local stimulation and measured with a multiterminal electrode. In some of the experiments extracellular [K+] ([K+]o) and transmembrane potentials were recorded. During normal perfusion vL and vT were (cm/sec) 50.08 +/- 2.13, (SE) and 21.08 +/- 0.97. After 3 to 5 min of global ischemia, vL and vT decreased to approximately 30 and 13 cm/sec. Before the occurrence of total inexcitability propagation became time dependent 2: 1 block developed and centrifugal spread from the stimulus site was partially blocked at short intervals and was normal at long intervals. This suggested that slowed conduction was dependent on spatial nonuniformities of recovery from excitability. Slowing of conduction during ischemia was not explained by accumulation of [K+]o alone, because vL and vT at a given [K+]o were lower during ischemia than during perfusion with elevated K+. In hearts perfused at 20 mM [K+]o "slow responses" were produced by addition of epinephrine (2.5 X 10(-5)M). Resting membrane potentials of slow responses were significantly lower than of depressed action potentials during ischemia. The values vL and vT of slow responses (10 and 5 cm/sec) were much lower than the lowest values during ischemia (20 and 10 cm/sec). This indicates that slow conduction in ischemia is associated with depressed action potentials initiated by a partially inactivated rapid Na+ inward current. The time dependence of nonuniform propagation and the relatively high conduction velocities explain two major characteristics of reentrant tachycardias in acute ischemia: the large diameters of reentrant circuits and the beat-to-beat changes in localization of conduction block.
Clinical trials evaluating platelet-modifying drugs in patients with atherosclerotic cardiovascular disease and thrombosis.
Authors: Harker L A
Published: June 2011

Aspirin has been convincingly shown to reduce stroke and death in men with transient ischemic attacks (it may possibly be beneficial to women also), myocardial infarction and death in patients with unstable angina, thromboembolic complications associated with artificial heart valves in patients receiving oral anticoagulants (although gastrointestinal bleeding is prohibitive with this combination), and thrombotic occlusion of silicone rubber arteriovenous cannulae in uremic patients undergoing hemodialysis. In addition, aspirin may possibly decrease occlusion of saphenous vein aortocoronary grafts and venous thrombosis in men after hip replacement, although these reports require confirmation. Aspirin is ineffective in the secondary prevention of stroke and has unproven benefit in the secondary prevention of myocardial infarction. Dipyridamole in combination with oral anticoagulation decreases the thromboembolic complications associated with mechanical heart valves. The combination of aspirin and dipyridamole prevents both early and late occlusion of saphenous vein aortocoronary bypass grafts and protects renal function in patients with membranoproliferative glomerulonephritis. The relative importance of combining aspirin and dipyridamole compared with either agent used singly remains to be established. Sulfinpyrazone reduces the thrombotic occlusion of arteriovenous cannulae and early occlusion of saphenous vein aortocoronary grafts. The reported benefit in the secondary prevention of myocardial infarction is controversial.
Interaction of platelets with the vessel wall in the pathophysiology of sudden cardiac death.
Authors: Hammon J W , Oates J A
Published: June 2011

The occurrence of ventricular fibrillation after occlusion of the circumflex coronary artery in the conscious dog was examined as one preparation for sudden cardiac death arising from coronary artery disease. The incidence of ventricular fibrillation after after circumflex occlusion was reduced from 53% to 6% (p less than .01) by the infusion of prostacyclin in doses that do not alter cardiac output or peripheral resistance. This effect of prostacyclin led to the evaluation of two structurally different inhibitors of thromboxane synthase in this preparation; RO 22-4679 and U-63557A reduced ventricular fibrillation by 82% and 100%, respectively (p less than .05). The inhibition of ventricular fibrillation by U-63557A was abrogated by pretreatment with indomethacin, suggesting that a metabolite of the endoperoxide that accumulated during thromboxane synthase inhibition was responsible for the protection from ventricular fibrillation.
Role of platelets and platelet inhibitors in aortocoronary artery vein-graft disease.
Authors: Fuster V , Chesebro J H
Published: June 2011

To study the prevention of occlusion of aortocoronary-artery bypass grafts, we conducted a prospective, randomized, double-blind trial comparing long-term administration of dipyridamole (begun 2 days before operation) plus aspirin (begun 7 hr after operation) with placebo in 407 patients. Results at 1 month and at 1 year showed a reduction in the rate of graft occlusion in patients receiving dipyridamole and aspirin. On the basis of our clinical trial and our experimental studies in dogs and pigs, we describe four consecutive phases of aortocoronary artery bypass vein-graft disease: an early postoperative phase of platelet thrombotic occlusion, which is significantly prevented by platelet inhibitor therapy when started in the perioperative period; in addition, occlusion rates are presently decreasing, perhaps related to better surgical and technical experience; an intermediate phase of platelet-related intimal hyperplasia, within the first postoperative year, which is not prevented with platelet inhibitor therapy; a late phase of occlusion, toward the end of the first postoperative year, in which intimal hyperplasia or complicating platelet thrombi superimposed on the intimal hyperplasia may contribute to occlusion; platelet inhibitor therapy is of significant benefit in the prevention of this thrombotic type of occlusion; a phase of atherosclerotic disease, after the first postoperative year, in which the role of platelets and of platelet inhibitor therapy is under investigation.
Pericardial effusion in the course of myocardial infarction: incidence, natural history, and clinical relevance.
Authors: Galve E , Garcia-Del-Castillo H , Evangelista A , Batlle J , Permanyer-Miralda G , Soler-Soler J
Published: June 2011

Incidence and significance of pericardial effusion in patients with acute myocardial infarction (AMI) have not been established. To evaluate these issues, we studied prospectively 138 consecutive patients with AMI. An echocardiogram was obtained in each 1, 3, and 10 days and 3 and 6 months after admission. Fifty four patients with unstable angina and 57 without heart disease were studied as controls. Echocardiographic diagnostic criteria of pericardial effusion were established from 33 additional patients undergoing surgery. Pericardial effusion was found in 28% of patients with AMI. Twenty-five percent of patients with AMI had pericardial effusion on the third day, vs 8% of patients with unstable angina (p less than .02) and 5% of patients without heart disease (p less than .01). At 1, 3, and 10 days and 3 and 6 months prevalence of pericardial effusion was 17%, 25%, 21%, 11%, and 8%, respectively. There was no case of tamponade. Pericardial effusion was more common in anterior AMI (p less than .02) and in patients with heart failure (p less than .05) but it was not significantly associated with early pericarditis, peak creatine kinase-MB, the level of anticoagulation, or mortality. Thus, pericardial effusion is a common event in patients with AMI (incidence of 28%), but does not result in specific complications. The reabsorption rate of pericardial effusion is slow and, in our experience, mild or moderate pericardial effusion does not preclude heparin therapy.
Intravenous recombinant tissue-type plasminogen activator in patients with acute myocardial infarction: a report from the NHLBI thrombolysis in myocardial infarction trial.
Authors: Williams D O , Borer J , Braunwald E , Chesebro J H , Cohen L S , Dalen J , Dodge H T , Francis C K , Knatterud G , Ludbrook P
Published: June 2011

The efficacy and safety of a 3 hr, 80 mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) were investigated in 47 patients with acute myocardial infarction. Coronary angiography, performed before the administration of rt-PA and for 90 min thereafter, demonstrated that 37 patients had total coronary occlusion before therapy. After 90 min of rt-PA (50 mg), reperfusion of the infarct-related artery was observed in 25 patients (68%). Continuous infusions of heparin for anticoagulation were administered for 8 to 10 days. Of 36 patients who underwent follow-up coronary cineangiography, 21 had initially presented with total occlusion and had experienced reperfusion at 90 min. Sustained perfusion of the infarct-related artery was observed in 14 (67%) of these 21 initially reperfused patients. Late angiography was performed in nine patients who initially demonstrated subtotal occlusion of the infarct-related artery; sustained perfusion was observed in eight (89%). Significant bleeding was observed in 15 patients (32%). A hematoma at the site of the acute catheterization accounted for most instances of significant bleeding (11/15, 73%). Administration of rt-PA resulted in a significant decline in fibrinogen and plasminogen while amounts of fibrin(ogen) degradation products rose. In no patient, however, did fibrinogen levels decline to less than 140 mg/dl. Thus, rt-PA, administered as a brief 80 mg intravenous infusion, is capable of restoring blood flow in a high proportion of patients with acute myocardial infarction due to total coronary obstruction. Declines in plasma fibrinogen and plasminogen are observed. If combined with heparin anticoagulation and invasive vascular procedures, significant bleeding is a common complication.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator: prevention by a maintenance infusion.
Authors: Gold H K , Leinbach R C , Garabedian H D , Yasuda T , Johns J A , Grossbard E B , Palacios I , Collen D
Published: June 2011

Twenty-nine patients with acute myocardial infarction were treated with recombinant human tissue-type plasminogen activator (rt-PA). The incidence of acute coronary reocclusion and its prevention by a maintenance infusion of rt-PA were studied. Intravenous rt-PA was given at a rate of 0.4 to 0.75 mg/kg over 60 to 120 min after angiographic documentation of complete coronary occlusion. Reperfusion was accomplished within 1 hr in 24 of 29 patients (83%) and was associated with a decrease of the plasma fibrinogen level by 20%. In a first group of 13 patients, 11 of whom were successfully reperfused, prevention of reocclusion was attempted with heparin anticoagulation. However, acute reocclusion within 1 hr after cessation of rt-PA was demonstrated angiographically in five of these patients (45%). Quantitative angiographic analysis indicated that acute reocclusion only occurred in patients with 80% or greater residual stenosis. In patients with less than 80% residual stenosis, heparin anticoagulation was sufficient to maintain patency during the hospital stay in four of five patients. In a second group of patients (n = 16), 13 of whom underwent reperfusion with intravenous rt-PA, seven demonstrated a residual stenosis of 80% or greater. These patients were given heparin and, in addition, 10 mg of rt-PA per hour for 4 hr. None developed acute angiographic reocclusion or clinical signs of reocclusion during the hospital stay. Repeat angiography at 10 to 14 days confirmed persistent patency in six of the seven patients. The maintenance infusion resulted in only a moderate additional drop in fibrinogen, while a steady-state plasma rt-PA level of 750 +/- 250 ng/ml was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergically mediated variations in the energy required to defibrillate the heart: observations in closed-chest, nonanesthetized dogs.
Authors: Ruffy R , Schechtman K , Monje E , Sandza J
Published: June 2011

The day-to-day variations in epicardial defibrillation threshold (DFT) were examined in closed-chest, unanesthetized dogs. In 11 animals, DFT decreased from 15.8 +/- 2.1 J (mean +/- SE) at the beginning of the study (day 1), to 7.4 +/- 1.7 J on day 2 (p less than .0001). DFT measured daily for 5 consecutive days in seven dogs decreased from 22.1 +/- 3.1 J on day 1 to 9.3 +/- 2.3 J on day 2 (p less than .01) and remained stable from day 2 to day 5. Transcardiac impedance, measured in six dogs, decreased from 112 +/- 6 omega on day 1 to 100 +/- 6 omega on day 2 (p = NS). Propranolol given on day 2 in 14 dogs increased DFT from 12.0 +/- 2.2 to 18.0 +/- 3.1 J (p less than .05). The effects on DFT of sequential administration of isoproterenol and propranolol were examined in 10 dogs. Isoproterenol decreased DFT from 10.0 +/- 1.9 to 5.5 +/- 1.5 J when given before propranolol (p less than .001, n = 10), and from 11.7 +/- 3.0 to 9.7 +/- 3.1 J when given after propranolol (p less than .05, n = 9). Propranolol increased DFT from 10.6 +/- 3.0 to 14.6 +/- 3.9 J when given before isoproterenol (p less than .02, n = 9), and from 10.7 +/- 1.4 to 14.4 +/- 1.5 J when given after isoproterenol (p less than .01, n = 10). These experiments demonstrate a sustained cardiac effect of epicardial defibrillation reflected by a decrease in DFT that is partially reversible by propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Loss of nocturnal decline in blood pressure after cardiac transplantation.
Authors: Reeves R A , Shapiro A P , Thompson M E , Johnsen A M
Published: June 2011

Twenty-four hour noninvasive ambulatory blood pressure and heart rate monitoring was performed on patients who underwent orthotopic cardiac transplantation, as part of the investigation of the de novo hypertension that developes in such patients. Patients with essential hypertension served as control subjects. The results demonstrated a highly significant loss of the usual decline in blood pressure and heart rate during sleep in the transplant patients. A similar loss of nocturnal decline in blood pressure was noted in a group of 10 patients with autonomic neuropathy secondary to diabetes mellitus. The de novo hypertension associated with cardiac transplantation is probably multicausal. Impairment of renal function by cyclosporin-A with associated salt and water retention and persistent elevation of the systemic vascular resistance in the presence of a restored normal cardiac output by the "new" heart are major factors. In addition, loss of the normal nocturnal decline in blood pressure and heart rate, which probably is related to the denervated state of the transplanted heart, may play an important role in blood pressure control.
Differential long-term intrarenal and neurohormonal effects of captopril and prazosin in patients with chronic congestive heart failure: importance of initial plasma renin activity.
Authors: Mettauer B , Rouleau J L , Bichet D , Kortas C , Manzini C , Tremblay G , Chatterjee K
Published: June 2011

Fifty patients with congestive heart failure received, by infusion, 15 ml/kg body weight water load, and systemic hemodynamic, renal function, and neurohumoral parameters values were measured before, 2 days, and 1 month after randomly allocating patients to prazosin or captopril therapy. Both prazosin and captopril caused similar and persistent hemodynamic changes, but important differences existed between their renal and neurohumoral effects. After 1 month of continuous therapy, captopril increased creatinine clearance from 71 to 84 ml/min/1.73(2) (p less than .05), increased the water load excreted in 5 hr from 50% to 71% (p less than .005), and increased 5 hr sodium excreted from 6.8 to 14.7 meq (p less than .005), Captopril also caused a decrease in plasma norepinephrine from 568 to 448 pg/ml (p less than .005), in plasma epinephrine from 94 to 73 pg/ml (p less than .05), and in plasma aldosterone from 57 to 28 ng/dl (p less than .005), without changing plasma vasopressin. These beneficial effects were greater after 1 month of therapy than after 2 days. The only beneficial effect of prazosin was to increase water excretion from 49% to 59% (p less than .05). The long-term response to captopril was similar in patients with higher (greater than 2.5 ng/ml/hr) and lower renin levels. However, in patients with lower renin levels, prazosin decreased pulmonary capillary wedge pressure (24.8 to 21.8 mm Hg, p less than .05), decreased plasma arginine vasopressin (1.16 to 0.75 pg/ml, p less than .05), increased water excretion (62% to 85%, p less than .005), and decreased plasma epinephrine (81 to 46 pg/ml, p less than .05), while in patients with higher renin levels none of these beneficial effects were noted. We conclude that captopril produces long-term beneficial renal and neurohumoral effects that prazosin does not despite similar hemodynamic changes with the two drugs, that these effects are at least partially dependent on the initial neurohumoral and hemodynamic status of the patient, and that through hemodynamic improvement vasodilators may chronically interrupt vasopressin overstimulation.
Analysis of coagulation and fibrinolysis during intravenous infusion of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction.
Authors: Collen D , Bounameaux H , De Cock F , Lijnen H R , Verstraete M
Published: June 2011

Coagulation and fibrinolysis were studied in patients with acute myocardial infarction during intravenous infusion of recombinant human tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 90 min, n = 101), streptokinase (1,500,000 IU over 60 min, n = 61), or placebo (n = 40). In the rt-PA group, the plasma level of rt-PA antigen was 1.2 +/- 0.6 micrograms/ml (mean +/- SD) and the euglobulin fibrinolytic activity (EFA) was 910 +/- 735 IU t-PA/ml. In the streptokinase group, the EFA was equivalent to 430 +/- 435 IU t-PA/ml. At the end of the infusion, the plasma fibrinogen level measured with a coagulation rate assay was decreased to 57 +/- 33% of the preinfusion value in the rt-PA group, to 7 +/- 10% in the streptokinase group, and remained unchanged in the placebo group. Fibrinogen-fibrin degradation products increased to 0.75 +/- 0.54 mg/ml in the streptokinase group but to only 0.10 +/- 0.13 mg/ml in the rt-PA group. The plasma levels of alpha 2-antiplasmin, plasminogen, and factor V decreased to between 30% and 45% in the rt-PA group but significantly more in the streptokinase group (to between 15% and 25%). Thus rt-PA induced much less systemic fibrinolytic activation than streptokinase. In the patients who received rt-PA, a weak correlation (r = .21, n = 89, .1 greater than p greater than .05) was found between the extent of fibrinogen breakdown at 90 min and the plasma rt-PA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Value and limitations of computer analysis of digital subtraction angiography in the assessment of coronary flow reserve.
Authors: Nissen S E , Elion J L , Booth D C , Evans J , DeMaria A N
Published: June 2011

Conventional coronary angiography has significant limitations in quantifying the severity and functional significance of coronary stenoses. However, coronary reactive hyperemia is an excellent physiologic indicator of coronary reserve. Digital subtraction angiography offers the potential to analyze coronary blood flow dynamics quantitatively. Therefore we assessed the accuracy of digital angiographic methods to detect and quantify reductions in coronary flow reserve secondary to stenoses of varying magnitude in an experimental canine preparation. Studies were performed in nine anesthetized open-chest dogs with an electromagnetic flow (EMF) probe and two pneumatic occluders positioned on the left circumflex coronary artery. One occluder served to induce reactive hyperemia by temporary total occlusion, while the other served to produce variable gradations of stenosis. Digital angiography was performed after the subselective injection of contrast under basal conditions and during reactive hyperemia. Time-intensity curves were obtained from digital angiograms for both a coronary and a myocardial region of interest. Measurements included area under the curve, time to peak contrast, and contrast disappearance rate. An index of coronary reserve was computed as the ratio of hyperemic to basal measurements for each of these methods. Coronary blood flow ranged from 6.5 to 142 ml/min, with hyperemic to basal EMF flow ratios of 0.80 to 4.2:1. The index derived from contrast decay rate showed a poor correlation with EMF (r = .34). The correlation between measurements of time to peak myocardial contrast and coronary blood flow was r = .68 (y = 0.16 x + 0.97). The area under the time-intensity curve from a coronary region of interest showed a close correlation with coronary blood flow (y = 0.91 x + 0.1, r = .86). Thus estimates of coronary reserve by computer analysis of digital subtraction angiograms can yield information regarding the physiologic consequences of coronary stenoses.
Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity.
Authors: Hasking G J , Esler M D , Jennings G L , Burton D , Johns J A , Korner P I
Published: June 2011

The analysis of plasma kinetics of the sympathetic neurotransmitter norepinephrine can be used to estimate sympathetic nervous "activity" (integrated nerve firing rate) for the body as a whole and for individual organs. In 12 patients with cardiac failure (left ventricular ejection fraction 10% to 39%), the mean arterial plasma norepinephrine concentration was 557 +/- 68 pg/ml (mean +/- SE) compared with 211 +/- 21 pg/ml in 15 subjects without heart failure (p less than .002). The difference was due to both increased release of norepinephrine to plasma (indicating increased "total" sympathetic activity) and reduced clearance of norepinephrine from plasma. The increase in sympathetic activity did not involve all organs equally. Cardiac (32 +/- 9 vs 5 +/- 1 ng/min; p less than .002) and renal (202 +/- 45 vs 66 +/- 9 ng/min; p = .002) norepinephrine spillover were increased by 540% and 206%, respectively, but norepinephrine spillover from the lungs was normal. Adrenomedullary activity was also increased in the patients with heart failure, whose mean arterial plasma epinephrine concentration was 181 +/- 38 pg/ml compared with 71 +/- 12 pg/ml in control subjects (p less than .02). There is marked regional variation, inapparent from measurements of plasma norepinephrine concentration, in sympathetic nerve activity in patients with congestive heart failure. The finding of increased cardiorenal norepinephrine spillover has important pathophysiologic and therapeutic implications.
Indium-111 platelet scintigraphy for the diagnosis of acute venous thrombosis.
Authors: Ezekowitz M D , Pope C F , Sostman H D , Smith E O , Glickman M , Rapoport S , Sniderman K W , Friedlaender G , Pelker R R , Taylor F B
Published: June 2011

Platelets labeled with indium-111 have been used successfully as a marker of active thrombosis in man. To establish the diagnostic accuracy of platelet scintigraphy in comparison to contrast venography in the diagnosis of acute lower limb venous thrombosis, we evaluated 103 consecutive patients divided into two groups. Platelets were labeled by the indium-111 oxine method. Patients from group I (n = 73, 56 had venograms) were asymptomatic and underwent platelet scintigraphy 1.1 +/- 0.6 days (mean +/- 1 SD) after a major orthopedic procedure. Patients from group II (n = 30, all had venograms) were symptomatic and underwent platelet scintigraphy 1.2 +/- 1.7 days after venography. In group II, 15 patients with positive findings on contrast venography were treated with intravenous heparin; five others with positive venograms did not receive heparin until platelet scintigraphy was completed. Both platelet scintigraphy and contrast venography were evaluated by two blinded observers. Only studies with blinded agreement of both platelet scintigraphy and contrast venography were included in the analysis. Sensitivity and specificity of platelet scintigraphy for the whole limb were 93% and 97% in group I and 42% and 67% in group II. The lower sensitivity in group II was most likely attributable to therapy with heparin. These results demonstrate that platelet scintigraphy, a test that permits imaging for up to five days after a single injection, correlates favorably with contrast venography in patients who have not received heparin and may be used as a surveillance test in high-risk patients. The role of platelet scintigraphy in acutely symptomatic patients requires further evaluation.
Improved selection of patients for programmed ventricular stimulation by frequency analysis of signal-averaged electrocardiograms.
Authors: Lindsay B D , Ambos H D , Schechtman K B , Cain M E
Published: June 2011

Improved selection of patients with suspected sustained ventricular tachycardia (VT) for programmed ventricular stimulation is needed. To determine if frequency analysis detects patients in whom sustained VT might be induced, we first obtained fast-Fourier transforms (FFT) of signal-averaged electrocardiograms (ECGs) from 20 patients with spontaneous sustained VT (group 1) and compared them with the results of programmed ventricular stimulation with single and double extrastimuli during two cycle lengths and burst pacing from two right ventricular sites. The FFT data were expressed as an area ratio that quantified the relative contributions of 20 to 50 Hz frequencies in the terminal QRS and ST segment. A logistic regression with inducibility as the dependent variable was used to help define area ratio values greater than 20 as abnormal. Sustained monomorphic VT was induced in 18 patients, each with an area ratio value greater than 20. Sustained VT was not induced in two patients, each with an area ratio value less than 20. FFT data were then compared prospectively with the results of programmed stimulation in 38 patients (group II) with nonsustained VT (12 patients) or syncope (26 patients) referred for electrophysiologic study. In none of the 26 patients in group II with normal FFT values was VT inducible. Sustained monomorphic VT was induced in five of 12 patients with abnormal FFT values. Thus, the results of FFT analysis correctly predicted the results of programmed ventricular stimulation in 88% of patients studied and in 82% of patients in group II with syncope or nonsustained VT. Moreover, all five patients in group II in whom sustained VT was induced were identified correctly.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial protection during transient coronary artery occlusion in man: beneficial effects of regional beta-adrenergic blockade.
Authors: Zalewski A , Goldberg S , Dervan J P , Slysh S , Maroko P R
Published: June 2011

The goal of this study was to verify whether myocardial protection could be achieved via the intracoronary administration of propranolol in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Accordingly, 21 patients undergoing PTCA were randomly assigned to receive either intracoronary placebo (group A, n = 10) or intracoronary propranolol (group B, n = 11). Three balloon inflations (i.e., coronary artery occlusions) were performed in each patient. Inflations I and II (maximum duration 60 sec) served as control occlusions. Inflation III (maximum duration 120 sec) was performed either after intracoronary administration of saline (2 ml) or propranolol (1.1 +/- 0.2 mg). The following electrocardiographic index of myocardial ischemic injury were measured: (1) time to development of ST segment elevation equal to 0.1 mV and (2) magnitude of ST segment elevation after 60 sec of coronary artery occlusion. Both indexes did not differ significantly between the groups during inflations I and II. In group A the time to development of ST segment elevation of 0.1 mV remained unchanged between the second and third occlusions (25 +/- 5 and 26 +/- 4 sec during inflations II and III, respectively). In group B subselective injection of propranolol into the affected coronary artery significantly prolonged the time to ST segment elevation of 0.1 mV from 19 +/- 4 sec (inflation II) to 53 +/- 9 sec (inflation III; p less than .001). Administration of placebo did not change the magnitude of ST segment elevation 60 sec after coronary artery occlusion between the second and third occlusion in group A (0.16 +/- 0.02 and 0.18 +/- 0.03 mV, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Relevance of location of defect and pulmonary vascular resistance to the intracardiac pattern of left-to-right shunt flow in dogs with experimental ventricular septal defect.
Authors: Okubo S , Nakai M , Tomino T
Published: June 2011

Left-to-right (L-R) shunting across a ventricular septal defect (VSD) often involves a direct VSD-pulmonary arterial component (jet) that surges from the VSD immediately into the pulmonary artery. We used the thermodilution technique in dogs with acute experimental VSD to quantify this component. In dogs with supracristal VSD (n = 7), the direct component represented 76 +/- 4% (mean +/- SE) of the total L-R shunt on average, vs 39 +/- 7% (p less than .001) of the total in dogs with infracristal VSD and the same level of L-R shunting (n = 6). The direct component can be expected to impose additional hyperkinetic forces on the pulmonary artery since it is driven by the left ventricular pressure. Although not yet clinically proven, we speculate therefore that patients with supracristal VSD may be at greater risk of becoming jeopardized by late-onset pulmonary vascular obstructive disease. Since a part of the total shunt other than the direct component dropped into the right ventricle, the right ventricle bore only 24% of the total shunt in supracristal VSD, but 61% in infracristal VSD. We also found that the amount of direct component was decreased, and therefore another part must have increased, as the pulmonary vascular resistance was artificially raised. As a second speculation, therefore, we suggest that patients with supracristal VSD may have less enlargement of the right ventricle than those with infracristal VSD before pulmonary hypertension develops.