Hemodynamic and volumetric response of the normal left ventricle to upright tilt testing.

The purpose of this study were to determine the specificity of the head-up tilt test in normal subjects when a graded isoproterenol infusion is used, and to evaluate the role of dynamic ventricular volume change during head-up tilt as a mechanism of syncope. We prospectively studied 12 normal volunteers, each of whom underwent an upright tilt test for 10 minutes at 80 degrees with and without an infusion of isoproterenol. A subgroup of five subjects had a third tilt test during administration of a combination of esmolol and isoproterenol. Blood pressure, heart rate, and left ventricular volumes and flow (obtained with Doppler echocardiography) were recorded in the following sequence: while supine, during upright tilt, while supine with isoproterenol, and during upright tilt with isoproterenol. During the initial head-up tilt, one subject had syncope. An additional eight subjects had presyncope or syncope during head-up tilt with isoproterenol. The remaining three subjects were asymptomatic. In subjects with syncope or near-syncope ("responders"), heart rate increased with isoproterenol but decreased markedly, to 76 +/- 5 beats/min, by the end of the protocol. Systolic blood pressure rose slightly above baseline during isoproterenol but fell from 118 +/- 4 to 85 +/- 5 mm Hg during head-up tilt with isoproterenol. The three asymptomatic subjects had only one significant change, an increase in heart rate with isoproterenol. In the five responders undergoing three tilt tests, left ventricular volume decreased significantly at end diastole (94 +/- 25 vs 58 +/- 22 ml) and end systole (34 +/- 13 vs 18 +/- 6 ml) when supine baseline is compared with initial upright tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

Immediate reproducibility of the tilt-table test in adults with unexplained syncope.

There are few data regarding the immediate reproducibility of the tilt-table test (TTT). Therefore, the immediate reproducibility of the TTT was examined in 19 patients (11 men and 8 women; mean age 49 +/- 19 years) with syncope or presyncope. The mean number of episodes that patients had experienced was 14 +/- 25 (range 1 to 100). After baseline supine observation for 10 minutes, patients were placed in 80 degrees of head-up tilt until a positive response occurred or for a maximum of 10 minutes. Patients were then returned to the supine position for 5 minutes, followed by retilt for another 10 minutes. If the baseline tilt was negative, the study was repeated with intravenous isoproterenol, and immediate reproducibility was examined in the same manner. The 19 patients underwent a total of 31 TTTs (19 baseline and 12 follow-up on drug). The TTT was immediately reproducible in 24 of 31 tests performed (77%). Eight tests were reproducibly positive and 16 negative. The results of 7 TTTs (23%) (5 baseline and 2 follow-up on drug) were not reproducible. In 6 of these studies (86%), the positive result occurred first and the negative result second. The reproducibility of an initially negative TTT result (16 of 17; 94%) was much higher than that of an initially positive one (8 of 14; 57%). The immediate reproducibility of the TTT in adult patients with unexplained syncope is approximately 75%. In studies that are not reproducible, most (86%) are positive first and negative second. Therefore, in most patients it is not necessary to check immediate reproducibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunology of a serum sickness/vasculitis reaction secondary to streptokinase used for acute myocardial infarction.

We have studied six patients who received streptokinase for acute myocardial infarction (MI). One of these patients experienced a serum sickness/vasculitis reaction nine days after receiving the drug. Immunologic investigation of serum obtained from these individuals demonstrated that IgE and IgG anti-streptokinase antibody concentrations (measured by radioimmunoassay) were significantly elevated, both pre and post (IgE antibody, 36-fold increase) drug exposure, in the individual having the serum sickness/vasculitis reaction. Two of five of the remaining MI patients receiving the drug had post-exposure elevation of IgE anti-streptokinase antibody, but no patient had the immunologic profile seen in the individual with vasculitis. One should be aware that the serum sickness/vasculitis reaction can occur late after administration of streptokinase when the acute MI patient is recuperating.

The automatic implantable cardioverter-defibrillator: efficacy, complications, and device failures.

Twenty-six patients with refractory ventricular arrhythmias received the automatic implantable cardioverter-defibrillator. A patch lead only was placed during arrhythmia surgery in 7 other patients. During 13 +/- 6 (SD) months, the device discharged in 10 patients because of a sustained ventricular arrhythmia. No sudden deaths occurred. There were 31 complications in 17 patients, including postoperative refractory heart failure, coronary artery erosion, subclavian vein thrombosis, postoperative stroke after conversion of atrial fibrillation, atelectasis with pneumonia, symptomatic pleural effusions, and infection at the generator site. The cardioverter-defibrillator discharged in 9 asymptomatic patients, failed to terminate ventricular fibrillation during postoperative testing in 3 patients, and had premature battery failure in 4 patients. Tachycardia slowing during chronic amiodarone therapy and unipolar ventricular pacing during ventricular fibrillation precluded or delayed arrhythmia sensing. Thus, the cardioverter-defibrillator can be life saving, but its potential complications and interactions with antiarrhythmic drugs and pacemakers must be considered at patient selection.

A potential method of correcting intracavitary left ventricular filling pressures for the effects of positive end-expiratory airway pressure.

Based on the observation that positive end-expiratory airway pressure (PEEP) causes comparable increments in intrapericardial and right-sided intracardiac pressures, we hypothesized that intracavitary left ventricular filling pressures measured in the presence of PEEP can be corrected for increased intrathoracic pressure by subtracting the effects of PEEP on intracavitary right ventricular filling pressures. Ventricular function curves (aortic blood flow vs intracavitary left ventricular end-diastolic pressure [LVEDP]) were generated with and without 15 cm of water of PEEP in eight dogs. All curves were shifted to the right by PEEP (i.e., intracavitary LVEDP was higher for any submaximal level of aortic blood flow). However, when pressures measured in the presence of PEEP were "corrected" by subtracting the corresponding increment in intracavitary right ventricular end-diastolic pressure caused by PEEP at each level of ventricular filling, control and corrected PEEP data points appeared to fall on the same curve in five dogs, and differed only slightly in three dogs. Mean control and corrected PEEP curves derived by averaging polynomial regression coefficients for each condition differed significantly from uncorrected PEEP curves (p less than .05), but not from each other. Analogous curves based on mean left atrial pressure were corrected equally well by subtracting the effects of PEEP on mean right atrial pressure. We conclude that the increments in intracavitary right heart filling pressures caused by PEEP can be used to correct intracavitary left heart filling pressures for the effects of PEEP on intrathoracic pressure.

Electrophysiologic evaluation and follow-up characteristics of patients with recurrent unexplained syncope and presyncope.

One hundred nineteen patients with unexplained syncope (82%) or presyncope (18%) underwent complete electrophysiologic study (EPS). Symptoms were recurrent in 72% of the patients. Fifty-two percent of the patients had structural heart disease. Forty-one patients had normal EPS results and 78 had electrophysiologic abnormalities (ventricular tachycardia in 31, induced atrial flutter/fibrillation in 17, vasovagal syncope in 8, hypersensitive carotid sinus syndrome in 7, supraventricular tachycardia in 6, heart block in 5 and sick sinus syndrome in 4). The presence of structural heart disease (p = 0.0033) and previous myocardial infarction (p = 0.05) were the only clinical or electrocardiographic predictors of a positive EPS response. Therapy was guided by EPS and patients were followed for 27 +/- 20 months (mean +/- standard deviation). In the patients with negative EPS results, 76 +/- 11% (mean +/- standard error) were symptom-free at follow-up, compared to 68 +/- 10% in the group with positive EPS responses. No clinical variables helped to predict remission in the absence of therapy. One patient in the negative EPS response group and 2 patients in the EPS positive group died suddenly (cumulative survival 94 +/- 4%). Total cardiovascular mortality was 13% in the positive EPS response group, and 4% in the negative EPS response group. Thus, certain clinical characteristics are helpful in selecting patients for study. Electrophysiologically guided therapy is associated with a recurrence and sudden death rate similar to an untreated control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Timing of the right ventricular apical electrogram during sustained ventricular tachycardia: relation to surface QRS morphology and potential clinical implications.

To evaluate the timing of the right ventricular (RV) apical electrogram in relation to the QRS complex during ventricular tachycardia (VT), 94 episodes of sustained uniform VT were analyzed in 56 patients. The timing of the RV apical electrogram varied and could be recorded from 33 ms before to 180 ms (mean 77 +/- 44 ms) after the onset of the QRS complex. The timing of the RV apical electrogram, expressed both as an absolute value and as a percentage of a QRS width, was significantly different when right bundle branch block (BBB) morphology VT (95 +/- 37 ms) and left BBB morphology VT (40 +/- 341) were compared (p less than 0.001). The timing of the RV apical electrogram, expressed as a percentage of the QRS width, was significantly different when VT with different axes were compared in the right BBB VT group (p less than 0.01). A left BBB VT, as compared to a right BBB VT, predicted an RV apical electrogram occurring in the first 35% of the QRS with a sensitivity of 74%, a specificity of 91%, and a positive predictive value of 84%. Right BBB VT with a right and inferior axis were usually associated with the latest occurring RV apical electrogram. A right BBB VT with a right and inferior axis predicted an RV apical electrogram inscribed in the latter half of the QRS with a sensitivity of 65%, a specificity of 84% and a positive predictive value of 80%.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of the fine structure of adeno-associated virus DNA with bacterial restriction endonucleases.

A physical map of the adeno-associated virus type 2 genome has been constructed on the basis of the five fragments produced by the restriction endonucleases HindII + III from Hemophilus influenzae. There are three endo R-HindII cleavage sites and one endo R-HindIII site. Evidence has been obtained to support the existence of two nucleotide sequence permutations in adeno-associated virus DNA, the start points of which have been estimated to be separated by 1% of the genome. The three cleavage fragments produced by endo R-Eco RI have been ordered and oriented with respect to the endo R-HindII + III cleavage map.

Promoter-like mutation affecting HPr and enzyme I of the phosphoenolpyruvate: sugar phosphotransferase system in Salmonella typhimurium.

A promoter-like mutation, ptsP160, has been identified which drastically reduces expression of the genes specifying two proteins, HPr and enzyme I, of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) in Salmonella typhimurium. This mutation lies between trzA, a gene specifying susceptibility to 1,2,4-triazole, and ptsH, the structural gene for HPr. It leads to a loss of active transport of those sugars that require the PTS for entry into the cell. Pseudorevertants of strains carrying this promoter-like mutation have additional lesions very closely linked to ptsP160 by transduction analysis and are noninducible for HPr and enzyme I above a basal level. Presumably, strains carrying ptsP160 are defective in the normal induction mechanism for HPr and enzyme I, and the pseudorevertants derived from them result from second-site initiation signals within or near this promoter-like element. The induction of HPr and enzyme I above their noninduced levels apparently is not required for transport of at least one PTS sugar, methyl alpha-d-glucopyranoside, since this sugar is taken up by the pseudorevertants at the same rate as by the wild type. The existence of a promoter-like element governing the coordinate inducibility of both HPr and enzyme I suggests that ptsH and ptsI constitute an operon. Wild-type levels of a sugar-specific PTS protein, factor III, are synthesized in response to the crr(+) gene in both a ptsP160 strain and its pseudorevertants; this suggests that the crr(+) gene has its own promoter distinct from ptsP.