bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure of atrial natriuretic factor to increase with volume expansion in acute and chronic congestive heart failure in the dog.
Authors: Redfield M M , Edwards B S , McGoon M D , Heublein D M , Aarhus L L , Burnett J C
Published: June 2011

It remains unclear whether the levels of atrial natriuretic factor (ANF) observed in chronic CHF are appropriate for the magnitude of elevations in atrial pressures. Specifically, it is not known whether acute increases in atrial pressure in CHF can result in further significant increases in circulating ANF. The present study was designed to test the hypothesis that in chronic CHF there is an attenuated relation between circulating ANF and atrial pressure such that the heart is unable to respond to further increases in atrial pressure with appropriate increases in ANF. Cardiovascular hemodynamics and plasma levels of ANF were measured at baseline and after rapid right ventricular pacing (RRVP) to produce acute (n = 10, 25 minutes RRVP) and chronic (n = 7, 14-16 days RRVP) CHF. Acute saline volume expansion was then performed in each group to determine the response of circulating ANF to acute increases in atrial pressure in both acute and chronic CHF. In chronic CHF, right atrial pressure was much higher than in acute CHF (8.5 +/- 0.9 vs. 3.4 +/- 1.3 mm Hg, p less than 0.05); however, circulating ANF was not greater in chronic as compared with acute CHF (385 +/- 73 vs. 500 +/- 89 pg/ml), which is consistent with an attenuated release of ANF in chronic CHF. In response to volume expansion, right atrial pressure increased in both acute (3.4 +/- 1.3 to 12.1 +/- 7 mm Hg) and chronic (8.5 +/- .9 to 13.3 +/- 1.0 mm Hg) CHF.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetics of myoglobin release and prediction of myocardial myoglobin depletion after coronary artery reperfusion.
Authors: Ellis A K , Saran B R
Published: June 2011

To better define the usefulness of blood myoglobin measurements in evaluating the effectiveness of attempted thrombolysis, we studied the kinetics of myoglobin entry into and removal from the circulation after coronary artery reperfusion and the relation between directly measured depletion of myocardial myoglobin after coronary occlusion and reperfusion and the amount of depletion predicted from plasma myoglobin concentration-time curves. Initially, canine myoglobin was administered to 11 dogs by both bolus injection and 40-minute infusion, and the subsequent disappearance patterns of myoglobin from plasma monitored by radioimmunoassay. A monoexponential regression line (corresponding to a one-compartment model) and a biexponential regression line (corresponding to a two-compartment model) were determined for each set of washout data, the kinetic parameters were calculated, and the goodness of fit of each model was assessed. Results were similar after both methods of myoglobin administration. In five of 11 animals, the one-compartment model described the myoglobin kinetics better; in the other six animals, the two-compartment model was statistically superior, but values for the volume of distribution and elimination rate constant differed by only 10% from the one-compartment estimates. After bolus administration of myoglobin and with a one-compartment model, the volume of distribution of myoglobin was determined to be 1,601 +/- 77 (SEM) ml, representing 6.8 +/- 0.2% of total body weight; the elimination rate constant averaged 0.132 +/- 0.006/min and corresponded to a mean half-time of disappearance of 5.5 +/- 0.2 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
pH-dependent effects of lidocaine on defibrillation energy requirements in dogs.
Authors: Echt D S , Cato E L , Coxe D R
Published: June 2011

Lidocaine increases the energy required for ventricular defibrillation in dogs. Because sodium channel-blocking agents that are weak bases have pH-dependent electrophysiologic effects, we investigated the pH dependence of lidocaine (pKa, 7.9) on internal defibrillation energy requirements in 28 dogs with atrial spring and left ventricular patch electrodes. Results of defibrillation testing were used to derive 50% and 90% successful energy requirements (ED50 and ED90) using logistic regression and were compared with analysis of variance. Acidosis produced by hydrochloric acid infusion decreased the arterial pH from 7.40 +/- 0.05 (SD) to 7.18 +/- 0.03 (n = 8, p less than 0.01), but no significant change in ED90 was observed (14 +/- 4 to 16 +/- 6 J). Lidocaine infusion to therapeutic levels (4.2 +/- .07 micrograms/ml) at normal pH (7.42 +/- 0.02) increased ED90 from 13 +/- 3 to 17 +/- 3 J (n = 6, p less than 0.05), and subsequent acidosis (pH 7.19 +/- 0.02, p less than 0.01) exacerbated this effect of lidocaine on ED90 (22 +/- 5 J, p less than 0.05). Alkalosis produced by respirator hyperventilation increased the arterial pH from 7.41 +/- 0.03 to 7.60 +/- 0.03 (n = 8, p less than 0.01), with a fall in ED90 from 13 +/- 4 to 8 +/- 3 J (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Opiate receptor inhibition improves the blunted baroreflex function in conscious dogs with right-sided congestive heart failure.
Authors: Sakamoto S , Liang C S
Published: June 2011

The endogenous opiate system is activated in congestive heart failure. because endogenous opioids are known to depress the baroreflex function, we conducted studies to determine whether the increased endogenous opioids play a role in causing the reduced baroreflex function that occurs in heart failure. Right-sided congestive heart failure was produced in 16 dogs by tricuspid avulsion and progressive pulmonary artery constriction. Seven sham-operated dogs were included for comparison. Baroreflex function was measured in the conscious dogs after pretreatment with either normal saline or an opiate-receptor antagonist by bolus administration of phenylephrine. The slope of the regression line relating systolic blood pressure to cardiac cycle (R-R) interval was taken as an index of baroreflex sensitivity. Plasma beta-endorphin was elevated in the dogs with heart failure (15.3 +/- 2.5 pmol/l) compared with the sham-operated dogs (4.2 +/- 0.4 pmol/l, p less than 0.001). The dogs with heart failure also exhibited a reduced baroreflex sensitivity (3.84 +/- 0.19 msec/mm Hg) after saline pretreatment when compared with the sham-operated dogs (10.86 +/- 1.20 msec/mm Hg, p less than 0.001). Administration of naloxone hydrochloride increased the baroreflex sensitivity of dogs with heart failure to 5.16 +/- 0.26 msec/mm Hg (p less than 0.01) but produced no significant effects in sham-operated dogs (11.36 +/- 1.42 msec/mm Hg). To further study the site of action for the effect of naloxone, we measured baroreflex sensitivity in the dogs with heart failure after pretreatment with naloxonazine, a selective mu-receptor antagonist, with ICI 154,129, a selective delta-receptor antagonist, or with naloxone methobromide, a quaternary analogue of naloxone that does not penetrate the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurement of end-systolic pressure-volume relations by intra-aortic balloon occlusion.
Authors: Gupta K B , Bavaria J E , Ratcliffe M B , Edmunds L H , Bogen D K
Published: June 2011

A new situ technique has been developed for measuring peak end-systolic elastance, Emax, that does not alter intrinsic or reflex-stimulated cardiac contractility. Afterload is varied by the inflation of an intra-aortic balloon catheter positioned in the ascending aorta. Balloon inflation is timed to interrupt ventricular ejection transiently at different times during the ejection phase, therefore, producing contraction at different ventricular volumes. Simultaneous measurement of left ventricular pressure and aortic flow during the occlusion sequence allows pressure versus ejected volume loops to be generated, from which the end-systolic pressure-volume relation is determined. End-systolic pressure-volume relation (ESPVR) was measured in six anesthetized Dorsett sheep with normal and enhanced contractile states. ESPVR was analyzed using both linear and nonlinear techniques. Although nonlinear components were seen in ESPVR, for the pressure-volume data range produced by the transient occlusions, linear approximations of ESPVR fit the end-systolic data points well. In the normal state, Emax, the slope of the linear ESPVR, was 1.01-5.08 mm Hg/ml in animals with body weights of 23-32 kg. After epinephrine infusion, Emax increased from 3.07 +/- 1.49 to 5.79 +/- 1.97 mm Hg/ml, which is consistent with previous investigations. Linear and nonlinear volume intercepts had a small increase with positive inotropic stimulation. Furthermore, serial measurements of Emax tracked cardiac function in depressed hearts with rapidly changing contractility.
Programmed electrical stimulation at potential ventricular reentry circuit sites. Comparison of observations in humans with predictions from computer simulations.
Authors: Stevenson W G , Nademanee K , Weiss J N , Wiener I , Baron K , Yeatman L A , Sherman C T
Published: June 2011

The purpose of this study was to define specific types of resetting responses to programmed electrical stimulation during human ventricular tachycardia and to use computer simulations of reentry circuits to assess the possible mechanisms and pacing site location relative to the reentry circuit for each type of response. The effects of scanning single stimuli at 35 left ventricular endocardial sites during sustained monomorphic ventricular tachycardia in 12 patients were studied. In considering alterations in QRS configuration and the delay between the stimulus and the advanced QRS, we identified three types of resetting responses to scanning stimuli consistent with stimulation at sites in or near the reentry circuit at 12 abnormal endocardial sites in eight patients. Type 1: all capturing stimuli were followed after a delay by early QRS complexes that had the same configuration as the tachycardia complexes. Type 2: late stimuli reset tachycardia as in type 1 but early stimuli reset the tachycardia after altering the QRS configuration. Type 3: late stimuli reset tachycardia as in type 1, but early stimuli advanced tachycardia with a short stimulus to QRS delay without altering the QRS configuration. In the simulations, premature depolarization of sites in the circuit produced orthodromic and antidromic wavefronts. The orthodromic wavefront propagated through the circuit and exited the circuit at the same site as did the previous tachycardia wavefronts and advanced the tachycardia without altering the configuration of the advanced QRS. The antidromic wavefront of relatively late stimuli was confined within or near the circuit by collision with the orthodromic wavefront of the preceding tachycardia beat and failed to alter ventricular activation distant from the circuit. Therefore, the QRS configuration after the stimulus was unchanged. A type 1 response occurred when all capturing stimuli produced this effect. However, with increasing stimulus prematurity, the antidromic wavefront propagated farther before colliding with an orthodromic wavefront, and under some conditions, it exited the circuit from a site other than the original circuit "exit," and altered the ventricular activation sequence distant from the circuit and, therefore, the QRS configuration, producing a type 2 pattern. The type 3 pattern occurred when the antidromic wavefront of early premature beats captured the original circuit exit. The effect of a stimulus was dependent on the stimulus prematurity, the relative conduction times from the stimulation site to the potential sites of "exit" from the circuit, and the timing of the excitable gap at the stimulation site.(ABSTRACT TRUNCATED AT 400 WORDS)
Usefulness of high-dose dipyridamole echocardiography test in coronary angioplasty.
Authors: Picano E , Pirelli S , Marzilli M , Faletra F , Lattanzi F , Campolo L , Massa D , Alberti A , Gara E , Distante A
Published: June 2011

Seventy-four consecutive patients with angina undergoing single-lesion percutaneous transluminal coronary angioplasty were evaluated with high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole echocardiography test (DET) before angioplasty and when possible, afterward. Angioplasty was clinically or angiographically successful in 63 patients and unsuccessful in 11. Before the procedure, 69 patients had a positive DET. Of these 69 patients, six with clinicall unsuccessful angioplasty had a dipyridamole time (i.e., the time from the onset of dipyridamole infusion to development of asynergy) lower than the 63 patients with clinically successfully angioplasty (4.2 +/- 2.9 vs. 7.0 +/- 2.9 minutes, mean +/- SD, p less than 0.01). In the five patients with angiographically unsuccessful angioplasty (residual stenosis diameter, greater than 50%), coronary stenosis decreased from 89 +/- 10 to 69 +/- 22 (p = NS); DET was positive in all five before and in four of the five after the procedure (100% vs. 80%, p = NS). In the 63 patients with angiographically successful angioplasty, coronary stenosis diameter was reduced from 85 +/- 9% to 30 +/- 10% (p less than 0.01). DET was positive in 58 patients before and in only 16 after the procedure (92% vs. 25%, p less than 0.01). In the 16 patients with positive DET, before and after angioplasty, dipyridamole time increased from 5.6 +/- 2.2 before to 7.3 +/- 2.4 minutes immediately after the procedure (p less than 0.05). After an average follow-up time of 10.8 +/- 5.9 months, angina recurred in eight of 47 patients with negative DET after angioplasty and in 11 of 16 patients with positive DET (17% vs. 69%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Neonatal critical valvar aortic stenosis. A comparison of surgical and balloon dilation therapy.
Authors: Zeevi B , Keane J F , Castaneda A R , Perry S B , Lock J E
Published: June 2011

Balloon aortic valvotomy (BAV) is an alternative to surgical valvotomy in infants and children. We compared BAV in 16 consecutive neonates (1985-1988) to surgical valvotomy in a prior group of 16 consecutive neonates (1978-1984). Both groups were comparable in terms of age, weight, hemodynamic data, left ventricular size, and associated lesions. There were six early and one late deaths after surgery. Five out of six neonates requiring a second operation died. Left ventricular size (measured in 13 neonates) had some influence on survival after surgery: three of three with small or hypoplastic left ventricles and three of 10 with normal-sized left ventricles died. After BAV, there were three early deaths, two patients who underwent stage I palliation of hypoplastic left heart syndrome, and two late deaths. As with surgical valvotomy, left ventricular size seemed to influence survival after BAV: five of six with small or hypoplastic left ventricles died or underwent stage I palliation for hypoplastic left heart syndrome and two of nine with normal-sized left ventricles died. At follow-up (26 +/- 17 months) in six patients in the surgical group, the peak systolic ejection gradient (PSEG) was 52.2 +/- 23 mm Hg and left ventricular end-diastolic pressure (LVEDP) 18.2 +/- 5.2 mm Hg. Aortic regurgitation was mild in five and moderate in the sixth patient. At follow-up (17.6 +/- 7.8 months) in nine patients in the balloon dilation group, the PSEG was 45.6 +/- 11 mm Hg in five patients at catheterization and 43.8 +/- 22.9 mm Hg in four patients by echocardiography-Doppler. Aortic regurgitation was mild in three and absent in the other six patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased morning incidence of myocardial infarction in the ISAM Study: absence with prior beta-adrenergic blockade. ISAM Study Group.
Authors: Willich S N , Linderer T , Wegscheider K , Leizorovicz A , Alamercery I , Schröder R
Published: June 2011

The time of acute myocardial infarction was determined in all 1,741 patients of the ISAM (Intravenous Streptokinase in Acute Myocardial Infarction) Study, based on onset of clinical symptoms and evaluation of plasma CK-MB enzyme time-activity curves. The incidence of myocardial infarction was markedly increased between 6:00 AM and 12:00 noon compared with other times of day (p less than 0.001). Myocardial infarction occurred 3.8 times more frequently between 8:00 and 9:00 AM (hour of maximum incidence) than between 12:00 midnight and 1:00 AM (hour of minimum incidence). Time of myocardial infarction based on clinical and enzymatic methods correlated well (r = 0.95). Patients with higher or lower left ventricular ejection fraction, higher or lower degree of wall motion abnormalities and residual stenosis of the coronary arteries, and one-, two-, or three-vessel disease exhibited a similar circadian pattern, suggesting that the morning is a risk period for patients with mild as well as severe coronary artery disease. Only the group of patients receiving beta-adrenergic blocking therapy before the event did not show an increased morning incidence of myocardial infarction. This observation may contribute to an understanding of the mechanisms by which beta-blockers reduce the incidence of myocardial infarction. Further investigation of physiologic changes occurring during the morning period of increased risk of myocardial infarction may lead to better understanding of the disorder. Design and timing of cardioprotective medication may play a crucial role in improving prevention of acute myocardial infarction.
Control of radiofrequency lesion size by power regulation.
Authors: Wittkampf F H , Hauer R N , Robles de Medina E O
Published: June 2011

The influence of power and exposure duration on lesion size in radiofrequency catheter ablation was investigated in 15 closed-chest dogs. Radiofrequency energy was delivered to the right ventricular endocardium between the tip of a standard 6F electrode catheter and a large W and durations of 5, 10, 20, 30, and 60 seconds. At necropsy 1 week later, well-demarcated homogeneous lesions were found when power had exceeded a threshold level that decreased from 1.8 W at 5 seconds to 0.7 W at 60 seconds. Lesion size ranged from 0 to 7.5 mm in depth and 0 to 9 mm in diameter. For the 5, 10, and 20 second ablations, lesion size was determined by exposure duration and power level. However, after a 20 second exposure, lesion size had reached maturity and was related to delivered power only. Therefore, a gradual, controlled growth of the lesion can be obtained by a stepwise increase of the radiofrequency power level with ample exposure duration at each level to allow for stabilization. At levels exceeding 7 W, the formation of a thin insulating layer of blood coagulum on the electrode surface caused an abrupt increase of impedance within approximately 30 seconds. Therefore, lesion size is limited to 8.5 mm in radiofrequency ablation with a standard 6F endocardial electrode catheter.
Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues.
Authors: Kloner R A , Przyklenk K , Whittaker P
Published: June 2011

Oxygen free radicals are known to be generated during periods of ischemia followed by reperfusion. There is still some controversy, however, concerning the use of electron paramagnetic resonance spectroscopy to accurately detect and identify the free radical species that are formed. There is no doubt that oxygen radicals are deleterious to the myocardium; free radicals cause left ventricular dysfunction and structural damage to myocytes and endothelial cells in both in vitro and in vivo preparations. Potential sources of these cytotoxic oxygen species include the xanthine oxidase pathway, activated neutrophils, mitochondria, and arachidonate metabolism, yet the crucial source of free radicals in the setting of ischemia and reperfusion is unresolved. There is little doubt that oxygen radicals play a role in the phenomenon of stunned myocardium induced by brief periods of ischemia followed by reperfusion; numerous studies have consistently observed that pretreatment with free radical scavengers and antioxidants enhances contractile function of stunned, postischemic tissue. Whether oxygen free radical scavengers administered only during reperfusion enhance recovery of stunned myocardium in models of brief ischemia remains to be determined. In models of prolonged ischemia (2 hours) followed by reperfusion, we have not observed a beneficial effect of scavengers on stunned myocardium. The issue of whether oxygen free radical scavengers are capable of reducing so-called irreversible or lethal reperfusion injury remains, in our opinion, unresolved. Although some studies have observed that agents such as superoxide dismutase and catalase reduce infarct size in ischemia and reperfusion models, many others have reported negative results. Additional studies will be needed to resolve this ongoing controversy. Oxygen free radicals may also contribute to reperfusion-induced arrhythmias in rodent heart preparations; however, less data are available in other animal models. The concept of reperfusion injury should not be considered a deterrent to reperfusion for the treatment of acute myocardial infarcts in the clinical setting. Thrombolytic therapy reduces myocardial infarct size, enhances recovery of left ventricular function, and improves survival. Whether incremental beneficial effects on these parameters will be obtained when oxygen radical-scavenging agents are used as adjuvant therapy to thrombolysis in patients remains to be determined.
Risk stratification of patients with non-Q wave myocardial infarction. The critical role of ST segment depression. The Diltiazem Reinfarction Study Research Group.
Authors: Schechtman K B , Capone R J , Kleiger R E , Gibson R S , Schwartz D J , Roberts R , Young P M , Boden W E
Published: June 2011

One-year follow-up data on 515 patients who survived hospitalization with MB-creatine kinase-confirmed, acute non-Q wave myocardial infarction were analyzed for factors related to mortality (n = 57) and late reinfarction (n = 64). Twelve of 24 analyzed variables were significantly associated with mortality. Those factors, which were independently predictive of mortality by Cox regression analysis, were persistent ST depression (p = 0.0009), a history of congestive heart failure (CHF) (p = 0.0069), older age (p = 0.0128), and ST elevation at hospital discharge (p = 0.0173). In-hospital reinfarction achieved borderline significance (p = 0.0512). Mortality during the follow-up period was 5.5% in patients with no ST depression, 10.1% in those with ST depression at baseline or discharge, and 22.2% in patients with ST depression at baseline and discharge (i.e., "persistent" ST depression). The age-adjusted risk of mortality for patients with persistent ST depression, discharge-ST elevation, and CHF was 13.99 times as high as was the risk for patients with no ST depression, no discharge-ST elevation, and no CHF. Of the 483 patients with complete electrocardiographic data at both baseline and discharge, 203 (42%) could be stratified into a high risk population with a risk ratio for 1-year mortality more than sevenfold that of patients with no risk factors. Although persistent ST depression was significantly associated with several measures of structural left ventricular damage, the independent significance of ST depression persisted even after adjusting for these factors. The independent predictors of late reinfarction (persistent ST depression, p = 0.0058; Killip class II or III, p = 0.0106; and left ventricular hypertrophy, p = 0.0470) permitted a similar risk stratification. We conclude that 1) easily identified clinical and electrocardiographic factors permit stratification of patients with non-Q wave infarction into high-risk subsets who may benefit from aggressive therapy; 2) ST depression is a highly significant and independent predictor of poor prognosis; and 3) the powerful predictive value of persistent ST depression suggests that non-Q wave myocardial infarction patients with this depression should be viewed as potentially high-risk patients who may be candidates for additional noninvasive testing or early coronary angiography.
Association of elevated anti-sarcolemma, anti-idiotype antibody levels with the clinical and pathologic expression of chronic Chagas myocarditis.
Authors: Sadigursky M , von Kreuter B F , Ling P Y , Santos-Buch C A
Published: June 2011

Antibody F(ab')2 fragments derived from the sera of four patients with histology-proven chronic Chagas myocarditis [cF(ab')2]-complexed antibody F(ab')2 fragments of children with acute Trypanosoma cruzi infection [aF(ab')2] in significantly higher molar ratios than those measured with F(ab')2 antibody fragments of normal subjects [nF(ab')2] from nonendemic areas (p less than 0.05). Anti-idiotype [cF(ab')2 X aF(ab')2] immune-complex formation was significantly blunted by preabsorption of cF(ab')2 with porcine heart atria sarcolemma (PAMs) immobilized on sepharose beads (inhibition, mean, 78.1 +/- 2.4%, n = 4). cF(ab')2 X nF(ab')2] immune-complex formation was also inhibited by pretreatment of cF(ab')2 with PAMs (inhibition, mean, 48.7 +/- 7.5%, n = 4). The sera of three groups of subjects from a geographic zone endemic for T. cruzi infection in the northeast of Brazil were assayed for free and immune-complexed IgG anti-acute T. cruzi infection F(ab')2. The indexed levels of free IgG anti-idiotype antibody activity and levels of IgG anti-idiotype immune complexes (IC') were markedly elevated in hospitalized patients with severe, decompensated chronic Chagas myocarditis (n = 23), and their IC' indexes were significantly higher than those measured in asymptomatic seropositive subjects from a nearby endemic village of the northeast of Brazil (Moniz Ferreira, n = 92, p less than 0.001) and in healthy seronegative villagers (n = 84, p less than 0.001). There exists a strong correlation between elevated IgG anti-sarcolemma, anti-idiotype activity levels and the clinical and pathologic expression of chronic Chagas myocarditis.
Inverse relation between serum cotinine concentration and blood pressure in cigarette smokers.
Authors: Benowitz N L , Sharp D S
Published: June 2011

Blood pressure is, on average, lower in cigarette smokers than in nonsmokers. In a cross-sectional study of 288 normotensive bus drivers, we found a significant inverse correlation between serum cotinine (the major metabolite of nicotine) and systolic and diastolic blood pressure that could not be accounted for by age, body weight, or alcohol consumption. Over the observed range of cotinine values, the average decrease in blood pressure was 10.7 and 7.0 mm Hg for systolic and diastolic blood pressures, respectively. We suggest that cotinine be measured to assess the influence of cigarette smoking in epidemiologic studies of blood pressure.
Action potential duration alternans in dog Purkinje and ventricular muscle fibers. Further evidence in support of two different mechanisms.
Authors: Saitoh H , Bailey J C , Surawicz B
Published: June 2011

An abrupt shortening of cycle length causes action potential duration (APD) alternation in both canine Purkinje (P) and ventricular (V) muscle fibers. Our recent study suggested that APD alternans is determined by the process controlling APD during electrical restitution in P but not in V fibers. In the latter, alternans was attributed to changes in the availability of intracellular calcium [Ca2+]i. We examined this hypothesis further with the following pharmacologic probes known to alter restitution or action of [Ca2+]i: tetradotoxin (0.5-3.0 microM), lidocaine HCl (2.0-12.0 micrograms/ml), sotalol (10 microM), nicorandil (10-20 microM), 4-amino-pyridine (0.5 microM), ryanodine (10 microM), caffeine (2 mM), and ARL 115 BS (100 microM). Alternans in P fibers persisted under all studied conditions but varied in magnitude depending on the time constant and amplitude of restitution. In V fibers, the magnitude of alternans did not correlate with APD changes during restitution, and APD alternans was associated with the alternans of action potential shape and alternans of developed tension. Alternans in V was suppressed by caffeine at 2.0 mM [Ca2+]o when tension was increased and by ryanodine at 1.0 mM [Ca2+]o when tension was decreased. Alternans in V was not altered by changes in [Ca2+]o within the range of 1.0-4.0 mM; by ARL 115 BS, a compound that increases myofibrillar sensitivity to calcium; or by any other pharmacologic probes. We concluded that in P fibers, APD alternans was determined by the factors controlling APD in the absence of alternans; V fibers posses an independent mechanism of alternans linked to alternans of tension and controlled by [Ca2+]i; in V fibers, alternans could be suppressed by both positive and negative inotropic interventions; and calcium released from sarcoplasmic reticulum plays an important role in the V alternans.
Aortic stenosis in elderly patients aged 80 or older. Treatment by percutaneous balloon valvuloplasty in a series of 92 cases.
Authors: Letac B , Cribier A , Koning R , Lefebvre E
Published: June 2011

Very elderly patients with severe aortic stenosis will probably benefit from percutaneous balloon valvuloplasty. Ninety-two patients, aged 80 or older (mean age, 84 +/- 3.7 years) and all severely incapacitated (18 with an associated pathologic condition or in critical condition with terminal heart failure), underwent a valvuloplasty procedure. Femoral access was used in all cases except seven (8%), in whom the femoral route had to be abandoned and the brachial approach was used due to severe arterial tortuosity. Peak-to-peak ventriculoaortic gradient decreased from 71 +/- 27 to 27 +/- 15 mm Hg, and the aortic valve area increased from 0.48 +/- 0.16 to 0.91 +/- 0.35 cm2 (p less than 0.01). Thirty-two percent had a postprocedure aortic valve area more than or equal to 1 cm2. The final valve area was less than or equal to 0.7 cm2 in 30% of the patients. There were three deaths (ages, 82, 92, and 98 years) in the procedure room. One stroke occurred 1 day after the procedure. Hematoma or thrombosis at the femoral puncture site was observed in 14 cases (15%), requiring surgical repair in only five cases. Three patients died in the hospital; the total in-hospital mortality was 6.5%. Among the 62 patients about whom information could be obtained at a mean follow-up interval of 13 +/- 5 months, there were 18 late deaths (mean age, 85 +/- 11 years). The majority of the surviving 44 patients experienced marked symptomatic improvement. The results indicate that balloon valvuloplasty can be offered to very elderly patients with severe aortic stenosis and can produce improvement in hemodynamic and clinical status.
Electrophysiologic effects of dipyridamole on atrioventricular nodal conduction and supraventricular tachycardia. Role of endogenous adenosine.
Authors: Lerman B B , Wesley R C , Belardinelli L
Published: June 2011

Exogenous adenosine has been shown to have potent electrophysiologic effects and antiarrhythmic properties within the atrioventricular (AV) node. Endogenous adenosine, a nucleoside with an increased release signaled by ischemia and hypoxia, is not believed to exert significant effects during homeostatic conditions. Recent experimental evidence suggests, however, that under normoxic conditions, the amount of adenosine released may be sufficient to mediate some of its physiologic effects. This study was designed to test the hypothesis that in humans the electrophysiologic effects of endogenously released adenosine on AV nodal conduction can be demonstrated under normoxic conditions by inhibiting uptake and degradation of the nucleoside. In the first protocol, the effects of intravenous dipyridamole (0.56 mg/kg bolus i.v., 5 micrograms/kg/minute infusion), a nucleoside-transport blocker that elevates endogenous plasma levels of adenosine, on AV nodal conduction were evaluated in seven patients. At a constant atrial paced cycle length, dipyridamole increased the AH interval from 110 +/- 19 to 164 +/- 26 msec, p = 0.002 (+/- SEM). Aminophylline (5.6 mg/kg i.v.), a competitive antagonist of adenosine, completely reversed the effects of dipyridamole on AV nodal conduction. Similarly, dipyridamole increased the cycle length at which pacing-induced AV nodal Wenckebach occurred, from 348 +/- 31 (control) to 388 +/- 33 msec (dipyridamole) (p = 0.002). In a second protocol, the effects of intravenous dipyridamole were evaluated in another group of six patients who had supraventricular tachycardia (SVT) in which the AV node was part of the reentrant circuit.(ABSTRACT TRUNCATED AT 250 WORDS)
Alpha 2-receptor-mediated vasoconstriction in patients with congestive heart failure.
Authors: Kubo S H , Rector T S , Heifetz S M , Cohn J N
Published: June 2011

alpha 2-Adrenoceptors exist postsynaptically to subserve vasoconstriction and presynaptically to modulate norepinephrine release into the synaptic cleft. Because adrenoceptors may down-regulate in response to chronic stimulation, we investigated the activity of alpha 2-receptor-mediated vasoconstriction in patients with congestive heart failure, who had increased levels of plasma norepinephrine. We used the isolated forearm model and intra-arterial infusions of subsystemic doses of yohimbine, a specific alpha 2-blocker, in 11 patients with heart failure and in 15 normal subjects. Yohimbine produced a dose-related increase in forearm blood flow and decrease in forearm vascular resistance. These findings were consistent with a direct vasodilator effect mediated by blockade of the postsynaptic alpha 2-vascular receptor. Furthermore, the vasodilator responses in patients with heart failure were similar to the normal subjects in terms of the percent increase in forearm blood flow, the dose-response relation, and the fractional response to hyperemia and phentolamine; thus, alpha 2-receptor-mediated vasoconstriction is neither enhanced nor down-regulated in heart failure. In addition, in patients with heart failure and in normal subjects, yohimbine produced an increase in the forearm venous norepinephrine concentration, consistent with an inhibition of the presynaptic alpha 2-receptor resulting in an augmented release of norepinephrine into the synaptic cleft. Thus, these data suggest that the postsynaptic alpha 2-receptor is an important mediator of vasoconstriction in patients with heart failure. Despite chronic elevations in plasma norepinephrine in patients with heart failure, alpha 2-receptor mechanisms subserving vasoconstriction and inhibition of norepinephrine release into the synaptic cleft are still functional in heart failure.
Diverse mechanisms of unexpected cardiac arrest in advanced heart failure.
Authors: Luu M , Stevenson W G , Stevenson L W , Baron K , Walden J
Published: June 2011

To define the mechanisms of unexpected cardiac arrest in advanced heart failure, we reviewed the causes of cardiac arrest as established from electrocardiographic monitoring and from clinical and autopsy data in patients hospitalized for cardiac transplantation evaluation and management of advanced heart failure (mean left ventricular ejection fraction, 0.18 +/- 0.08) who were stable while on vasodilator and diuretic therapy such that hospital discharge to home was anticipated. Twenty-one cardiac arrests occurred in 20 of 216 (9%) such patients during a 4-year period. Heart failure was due to coronary artery disease with prior myocardial infarction in 13 patients and nonischemic cardiomyopathy in seven patients. The rhythm at the time of arrest was severe bradycardia or electromechanical dissociation (BA/EMD) in 13 (62%) patients. The precipitating cause of the BA/EMD arrest was coronary artery thrombosis or embolism in two patients, pulmonary embolism in one patient, hyperkalemia in two patients, and unexplained hypoglycemia in one patient. In seven of 13 (54%) patients, a precipitating cause of the bradycardia arrest could not be established. Only eight of 21 (38%) arrests were due to ventricular tachycardia or fibrillation (VT/VF), and all occurred in patients with prior myocardial infarction (p = 0.02 vs. BA/EMD arrests). Two VT/VF arrests were due to acute or recent infarction, and one patient had hyperkalemia. The patients who suffered a BA/EMD arrest were similar to those who had a VT/VF arrest in age, ventricular arrhythmia history, ventricular function, and serum potassium levels. Serum sodium levels were lower in patients with BA/EMD arrests (129 +/- 3 vs. 133 +/- 4 meq/l, p = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
Beta 2-microglobulin. A reliable parameter for differentiating between graft rejection and severe infection after cardiac transplantation.
Authors: Teufelsbauer H , Prischl F C , Havel M , Holzinger C , Lion T , Schwarzmeier J D , Laczkovics A
Published: June 2011

We investigated the role of beta 2-microglobulin as a noninvasive parameter to monitor acute rejection and severe infection in 45 consecutive heart transplant recipients. Endomyocardial biopsy revealed moderate (41 patients) or severe (three patients) rejection in 44 patients. Severe infections of bacterial septicemia (11 patients), bronchopneumonia (two patients), and viral infection (seven patients) were detected by a meticulous schedule of various clinical and laboratory tests. beta 2-Microglobulin levels in serum, generally corrected for serum creatinine, were significantly elevated in patients with infections (median, 6.3 mg/l; range Q10-Q90, 3.47-10.27 mg/l) compared with levels in patients with rejection (p less than 0.0001) or in patients in obviously good condition (p less than 0.0001). At the onset of acute rejection, the median corrected beta 2-microglobulin serum level was 1.56 mg/l (range Q10-Q90, -0.05-3.46 mg/l) and was significantly different from the control group (p less than 0.01). In addition, density function and empirical quantile analyses allowed us to define ranges of beta 2-microglobulin levels that would differentiate between rejection (2.05-3.46 mg/l) and infection (greater than 3.46 mg/l). With these values, sensitivity and specificity were 0.9 and 0.938 for detection of infection and 0.23 and 0.925 for detection of rejection, respectively. By means of beta 2-microglobulin, two cases of infection were misinterpreted as rejection (10%), and four of 44 rejections were mistaken for infections (9%). We conclude that measurements of beta 2-microglobulin may improve the management of heart transplant patients.
Platelet and vascular function during coronary thrombolysis with tissue-type plasminogen activator.
Authors: Kerins D M , Roy L , FitzGerald G A , Fitzgerald D J
Published: June 2011

Platelet activation may limit the response to tissue-type plasminogen activator (t-PA) during coronary thrombolysis in humans. As an index of platelet activation, we assessed thromboxane A2 biosynthesis during coronary thrombolysis with intravenous t-PA in patients with acute myocardial infarction. Urinary 2,3-dinor-thromboxane B2, a metabolite of thromboxane A2, was increased to a peak of 3,327 +/- 511 pg/mg creatinine (n = 12) following administration of intravenous t-PA and remained elevated for 48 hours. This increase was abolished by pretreatment with aspirin 325 mg orally (n = 6), indicating de novo biosynthesis of thromboxane A2 rather than washout of preformed metabolites during reperfusion. Prostacyclin (PGI2) biosynthesis, determined by excretion of 2,3-dinor-6-keto-PGF1 alpha, also increased after t-PA administration. However, this increase was less pronounced in patients who reperfused (28 +/- 3.3 ng.hr/mg creatinine) than in patients who failed to reperfuse (118 +/- 30 ng.hr/mg creatinine, p less than 0.05). These data provide evidence of platelet activation during coronary thrombolysis with t-PA. In patients who reperfuse, the reduction in PGI2 biosynthesis may be a marker of reperfusion injury to the vasculature and may further amplify platelet activation.
Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors.
Authors: Coller B S , Folts J D , Smith S R , Scudder L E , Jordan R
Published: June 2011

We studied the dose-response effects of the F(ab')2 fragments of murine monoclonal antibodies to the platelet GPIIb/IIIa receptor (7E3 and 10E5) on in vivo platelet thrombus formation in a well-characterized monkey model in which the carotid artery is stenosed and thrombus formation is provoked and augmented by intimal damage and the infusion of subaggregating doses of epinephrine. Both antibodies abolished thrombus formation with a mean dose of -0.2 mg/kg. Ex vivo platelet aggregation was not always abolished at doses that abolished thrombus formation; similarly, bleeding times were only moderately prolonged (9.1 +/- 1.4 minutes) at these doses. Increasing the dose above that required to abolish thrombus formation consistently produced abolition of ex vivo platelet aggregation, marked prolongation of the bleeding time (14.2 +/- 1.5 minutes), and nearly quantitative blockade of GPIIb/IIIa receptors. We conclude that in a significant percentage of animals, the extent of GPIIb/IIIa blockade required to prevent vasoocclusive thrombus formation in this model is less than that required for abolition of platelet aggregation, and that the preservation of only a minority of functional GPIIb/IIIa receptors might be adequate to maintain a nearly normal bleeding time.
Verapamil preserves myocardial performance and energy metabolism in left ventricular hypertrophy following ischemia and reperfusion. Phosphorus 31 magnetic resonance spectroscopy study.
Authors: Buser P T , Wagner S , Wu S T , Derugin N , Parmley W W , Higgins C B , Wikman-Coffelt J
Published: June 2011

While calcium entry blockers have a beneficial influence on the postischemic recovery of the nonhypertrophied heart, their influence on the hypertrophied heart has not been determined. The aim of this study was to assess postischemic recovery of myocardial performance and energy metabolites in rat hearts with left ventricular hypertrophy pretreated either chronically or acutely with verapamil. Left ventricular hypertrophy was induced by suprarenal constriction of the abdominal aorta. Hemodynamics and phosphorus 31 magnetic resonance spectra were monitored simultaneously in the isolated hearts during control perfusion, after 30 minutes of global ischemia, and after 30 minutes of reperfusion. All hypertrophied hearts had significantly higher rate-pressure products than normal hearts. Compared with normal hearts, oxygen consumption was significantly lower in all hypertrophied hearts, especially untreated hypertrophied hearts. Also, before ischemia all normal or hypertrophied hearts (treated or untreated) began with comparable phosphorylation potentials (i.e., the supply of energy was not significantly different). Postischemic recovery was not related to energy supply-oxygen demand before onset of ischemia. Furthermore, it was not related to energy levels or intracellular pH during ischemia. For postischemic recovery, the rate-pressure product was 40 +/- 5% in the hypertrophied heart, 83 +/- 5% in the normal, 100 +/- 3% in the hypertrophied heart chronically treated with verapamil, and 82 +/- 5% in the hypertrophied heart acutely treated with verapamil. The degree of recovery was related to coronary flow both before and after ischemia. The latter is important for flushing deleterious metabolites and ions from the interstitial space as well as for delivery of oxygen and substrate to the myocardium.
Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow.
Authors: Ambrosio G , Weisman H F , Mannisi J A , Becker L C
Published: June 2011

The "no-reflow" phenomenon, the occurrence of areas with very low flow in hearts reperfused after ischemia, is thought to be largely established at the time of reperfusion as a result of microvascular damage induced by ischemia. In the present study we sought to determine whether additional impairment of tissue perfusion might also occur during the course of reperfusion. Open-chest dogs were subjected to 90 minutes of left circumflex coronary artery occlusion and reperfused for 2 minutes (n = 7) or 3.5 hours (n = 8). Myocardial perfusion was visualized in left ventricular slices following in vivo injection of the fluorescent dye thioflavin-S just before killing. The area of impaired perfusion (absent thioflavin) averaged 9.5 +/- 3.0% of the risk region in dogs reperfused for 2 minutes, whereas it was nearly three times as large in dogs reperfused for 3.5 hours (25.9 +/- 8.2% of the risk region, p less than 0.05). Serial measurements of flow by microspheres during reperfusion demonstrated zones within the postischemic myocardium that were hyperemic 2 minutes after reperfusion, with adequate flow still present at 30 minutes, but with a subsequent marked fall in perfusion. After 3.5 hours these areas showed negligible flow (0.13 +/- 0.3 ml/min/g) and no thioflavin uptake. Tissue samples showing postischemic impairment in perfusion has received virtually no collateral flow during ischemia (less than 0.01 ml/min/g), whereas collateral flow was significantly higher in adjacent thioflavin-positive zones (0.04 +/- 0.01 ml/min/g in endocardial samples and 0.07 +/- 0.02 ml/min/g in samples from the midmyocardium, p less than 0.001 vs. thioflavin-negative areas). Areas that showed late impairment of flow invariably demonstrated contraction band necrosis, which contrasted with the pattern of coagulation necrosis observed in areas of "true" (i.e., immediate) no-reflow. Intracapillary erythrocyte stasis and marked intravascular neutrophil accumulation (to levels greater than 20-fold that found after 2 minutes reperfusion) were typically observed in areas of delayed impairment to flow. Obstruction to flow at the capillary level was confirmed in additional dogs in which the heart was injected postmortem with silicone rubber to delineate the microvascular filling pattern. Areas of absent capillary filling were much more extensive after 3.5 hours than after 2 minutes reperfusion. Thus, this study shows that the occurrence of areas of markedly impaired perfusion in postischemic myocardium is related only in part to an inability to reperfuse certain areas on reflow. A more important factor is represented by a delayed, progressive fall in flow to areas that initially received adequate reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)
Trends in congenital heart disease in Dallas County births. 1971-1984.
Authors: Fixler D E , Pastor P , Chamberlin M , Sigman E , Eifler C W
Published: June 2011

To examine the changes in birth cohort prevalence rates and severity of congenital heart disease, we studied children with congenital heart disease born to blacks, whites, and Mexican-Americans in Dallas County from 1971 through 1984. Diagnoses were made by pediatric cardiologists' clinical evaluations, echocardiography, catheterization, surgery, or autopsy. During this study period, 2,509 of 379,561 liveborn infants were diagnosed, a prevalence rate of 6.6/1000. The rates for whites was significantly higher than for blacks or Mexican-Americans--7.2/1,000, 5.6/1,000, and 5.9/1,000, respectively. The rate for severe cases requiring cardiac catheterization or surgery or undergoing autopsy was 3.1/1,000 and did not differ among the three groups. The time trend for rates of congenital heart disease suggested an apparent increase in prevalence rate during the 1970s; however, the prevalence rate of severe forms remained relatively stable. This indicates that the apparent rise in prevalence could be accounted for by an increase in detection of mild cases. These findings were interpreted as reflecting a greater tendency for pediatricians to refer asymptomatic children with significant heart murmurs to a pediatric cardiologist.