Gamma-aminobutyric acid antagonism and presynaptic inhibition in the frog spinal cord.

The convulsant alkaloid bicuculline blocked presynaptic inhibition, dorsal root potentials, primary afferent depolarization, and depolarizing effects of gamma-aminobutyric acid on dorsal root terminals of the amphibian spinal cord, but did not block effects of other putative amino acid transmitters. These actions of bicuculline suggest that gamma-aminobutyric acid may be the transmitter involved in spinal presynaptic inhibition.

Programmed ventricular stimulation in patients with left ventricular dysfunction and ventricular tachycardia: effects of acute hemodynamic improvement due to nitroprusside.

To assess the electrophysiologic effects of acute hemodynamic improvement in patients with left ventricular systolic dysfunction, 12 patients with a left ventricular ejection fraction less than 0.40 and a history of sustained monomorphic ventricular tachycardia were studied. All patients had underlying coronary artery disease. Patients underwent programmed cardiac stimulation in random order during a baseline period and with nitroprusside infusion. Mean pulmonary capillary wedge pressure decreased from 20 +/- 8 mm Hg at baseline study to 8 +/- 3 mm Hg during nitroprusside infusion (p less than 0.0001). Pulmonary artery, right atrial and systemic arterial pressures also decreased with nitroprusside (p less than 0.01). Cardiac output did not change. Left ventricular dimensions, determined by two-dimensional echocardiography, decreased significantly during nitroprusside infusion. The right ventricular effective refractory period, measured during ventricular drive trains at cycle lengths of 400 and 600 ms, were similar during baseline and nitroprusside periods (271 +/- 30 versus 274 +/- 31 ms at 600 ms, and 249 +/- 25 versus 246 +/- 18 ms at 400 ms). In 2 patients no ventricular arrhythmias were induced during either study period; in the other 10, ventricular tachyarrhythmias were induced during both periods. The mean number of extrastimuli required to induce a ventricular tachyarrhythmia was similar during the baseline period (1.8 +/- 0.6) and during nitroprusside infusion (1.9 +/- 0.7). As well, the mean cycle length of ventricular tachycardia induced was similar during the baseline period (347 +/- 61 ms) and during nitroprusside infusion (342 +/- 70 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic assessment of patients with infectious endocarditis: prediction of risk for complications.

To enhance the echocardiographic identification of high risk lesions in patients with infectious endocarditis, the medical records and two-dimensional echocardiograms of 204 patients with this condition were analyzed. The occurrence of specific clinical complications was recorded and vegetations were assessed with respect to predetermined morphologic characteristics. The overall complication rates were roughly equivalent for patients with mitral (53%), aortic (62%), tricuspid (77%) and prosthetic valve (61%) vegetations, as well as for those with nonspecific valvular changes but no discrete vegetations (57%), although the distribution of specific complications varied considerably among these groups. There were significantly fewer complications in patients without discernible valvular abnormalities (27%). In native left-sided valve endocarditis, vegetation size, extent, mobility and consistency were all found to be significant univariate predictors of complications. In multivariate analysis, vegetation size, extent and mobility emerged as optimal predictors and an echocardiographic score based on these factors predicted the occurrence of complications with 70% sensitivity and 92% specificity in mitral valve endocarditis and with 76% sensitivity and 62% specificity in aortic valve endocarditis.

Right coronary artery stenosis: an independent predictor of atrial fibrillation after coronary artery bypass surgery.

OBJECTIVES: This study attempted to determine the importance of severe proximal right coronary artery disease as a predictor of atrial fibrillation in patients after coronary artery bypass surgery. BACKGROUND: Studies in patients undergoing noncardiac surgery have suggested that ischemia in the right coronary artery distribution is associated with a high incidence of atrial fibrillation. However, the importance of right coronary artery disease as a predictor of atrial fibrillation after bypass surgery is unknown. METHODS: The occurrence of sustained postoperative atrial fibrillation was studied prospectively in 168 consecutive patients undergoing coronary artery bypass grafting. Patients were followed up postoperatively until discharge. Severe right coronary artery stenosis was defined as > or = 70% lumen narrowing. RESULTS: Of 104 patients with proximal or mid right coronary artery stenosis, 45 (43%) had atrial fibrillation postoperatively compared with 12 (19%) of the 64 patients without significant right coronary disease (p = 0.001). Univariate predictors of atrial fibrillation included right coronary artery stenosis (p = 0.001), advancing age (p = 0.0001) and lack of beta-adrenergic blocking agent therapy after bypass surgery (p = 0.0004). Multivariate adjusted risk of developing atrial fibrillation after bypass surgery increased with the presence of severe right coronary artery disease (odds ratio 3.69, 95% confidence interval [CI] 1.61 to 8.48), advancing age (odds ratio 2.24/10 years, CI 1.48 to 3.41) and male gender (odds ratio 2.36, CI 1.01 to 5.49). The use of beta-blockers postoperatively was associated with a protective effect (odds ratio 0.4, CI 0.17 to 0.80). CONCLUSIONS: The presence of severe right coronary artery stenosis is an independent and powerful predictor of atrial fibrillation after coronary artery bypass surgery. In association with age, gender and postoperative beta-blocker therapy, these variables can be used to identify patients at increased risk for developing this arrhythmia.

Increased left ventricular diastolic chamber stiffness immediately after coronary artery bypass surgery.

OBJECTIVES: The aim of this study was to assess the incidence and severity of left ventricular diastolic dysfunction immediately after coronary artery bypass surgery by utilizing simultaneous transesophageal echocardiographic and hemodynamic monitoring. BACKGROUND: Left ventricular diastolic dysfunction has been documented after coronary bypass surgery, but its measurement has been technically difficult to acquire and limited by dependence on loading conditions. METHODS: End-diastolic pressure-area curves were constructed before and immediately after coronary bypass surgery in 20 patients. Transesophageal echocardiographic images at the midpapillary level of the left ventricle and hemodynamic data were recorded. Volume status was manipulated to alter loading conditions, and multiple measurements were taken at each loading condition. RESULTS: Diastolic function worsened in all patients, as manifested by a postoperative leftward shift of the end-diastolic pressure-area curve. At a comparable preload, mean end-diastolic area +/- SEM decreased by 15% from 17.6 +/- 0.8 to 14.9 +/- 0.8 cm2 postoperatively (p = 0.0001). CONCLUSIONS: Left ventricular diastolic chamber stiffness frequently increases immediately after coronary artery bypass surgery. Simultaneous hemodynamic and transesophageal echocardiographic monitoring, through the construction of end-diastolic pressure-area curves, is a useful method to evaluate diastolic function and guide management after cardiac surgery.

Evolution of the temporal contraction sequence after acute experimental myocardial infarction.

The effect of infarct maturation on the temporal sequence of contraction within infarct zones has not previously been described. Accordingly, the time-varying pattern of contraction within ischemic/infarct zones was studied with use of cross-sectional echocardiography in 17 dogs at 10 min to 6 weeks after acute experimental myocardial infarction. Left ventricular short-axis images were digitized from end-diastole to end-systole and endocardial fractional radial change along 36 evenly spaced rays was calculated. The circumferential extent of dyskinesia and the number of rays that exhibited maximal dyskinesia were determined for each decile of the normalized contraction sequence. Between 10 min and 1 week after infarction, the greatest circumferential extent of dyskinesia occurred between the 3rd and 4th deciles of the normalized contraction sequence. However, as the infarct matured, the greatest spatial expanse of dyskinesia was noted to occur progressively earlier in the contraction sequence (second decile at 6 weeks), and the extent of mid- to late-systolic dyskinesia decreased markedly. Whereas end-systolic dyskinesia was present in 30% to 50% of ischemic/infarct zone rays from 10 min to 48 h, end-systolic dyskinesia was no longer observed at 6 weeks. Similarly, the maximal amplitude of dyskinesia was most commonly observed during midsystole from 10 min to 48 h, but occurred progressively earlier as the infarct matured, falling during the first decile at 6 weeks after infarction. These data suggest that maximal circumferential extent and amplitude of dyskinesia occur progressively earlier in the systolic contraction sequence as the infarct matures.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of embolic events after cardioversion of atrial fibrillation. Current and evolving strategies.

We review the incidence of embolic events following cardioversion of atrial fibrillation, as well as the literature that forms the basis for the current strategy of anticoagulation before, and following, cardioversion to reduce the risk of post-cardioversion embolism. We evaluate a new strategy that uses transesophageal echocardiography to identify patients in atrial fibrillation without atrial thrombi who may be safely cardioverted without preceding anticoagulation and we also address the embolic event and anticoagulation issues in patients with atrial flutter. Cardioversion of atrial fibrillation to sinus rhythm is associated with a small but significant risk of thromboembolic events (average incidence, 1.5%; range, 0% to 7%). Anticoagulating these patients before cardioversion appears to significantly reduce this risk, and because of the delay in return of atrial contraction, anticoagulation should be continued for several weeks following cardioversion. The current guidelines for anticoagulating patients in atrial fibrillation who are to be cardioverted is based primarily on clinical observations, numerous uncontrolled case series, two retrospective trials, and one prospective nonrandomized controlled trial. Anticoagulation for 3 weeks before cardioversion followed by 4 weeks of anticoagulation after cardioversion is a theoretically sound and effective approach to reduce the risk of thromboembolic events. The use of transesophageal echocardiography to rule out thrombus and thus identify low-risk patients who may undergo cardioversion without preceding anticoagulation has been supported by several small studies that successfully used this strategy. However, the demonstration of a postcardioversion atrial and atrial appendage "stunning" suggests that anticoagulation needs to be given at the time of, and following, cardioversion. While promising, this transesophageal echocardiography--guided strategy for cardioversion of patients in atrial fibrillation requires more rigorous study before its routine use can be recommended. The current management of pure atrial flutter requires no anticoagulation before cardioversion; however, several clinical observation suggest theoretical risks for embolic events in these patients, thus further investigation of this strategy may be warranted.

Echocardiographic examination of women previously treated with fenfluramine: long-term follow-up of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Fenfluramine hydrochloride was withdrawn from the market in September 1997 after reports of heart valve abnormalities in patients who used it. The prevalence of echocardiographic abnormalities and the clinical cardiovascular status of patients who received fenfluramine monotherapy remains uncertain. METHODS: A long-term, follow-up evaluation was undertaken in subjects who were randomly assigned to receive either fenfluramine hydrochloride (60 mg daily) or placebo as part of a double-blind smoking cessation therapy study. Cardiovascular status was evaluated by echocardiography, medical history, and physical examination. RESULTS: From the group of 720 smokers who had originally participated in the smoking cessation therapy trial, 619 women were enrolled; data from 530 (276 in the fenfluramine group and 254 in the placebo group) were evaluable. No statistically significant differences were identified in the prevalence of aortic or mitral regurgitation by Food and Drug Administration criteria or by grade, aortic or mitral valve leaflet mobility restriction or thickening, elevated pulmonary artery systolic pressure, or abnormal left ventricular ejection fraction. No significant differences were demonstrated in cardiovascular status by physical examination, and no serious cardiac events were noted among fenfluramine-treated subjects. CONCLUSION: There was no evidence of drug-related heart disease up to 4.9 years after anorexigen therapy in subjects who were randomly assigned to receive fenfluramine at the recommended dose for up to 3 months.

Skeletal muscle tone and the misunderstood stretch reflex.

This review presents a revision of long-accepted tenets regarding the genesis of muscle tone in humans. Most discussions liken muscle tone in humans to the reflex tone described by Sherrington in decerebrate animals. That tradition presumes that muscle tone is fully determined by the monosynaptic stretch reflex, that tonic fusimotor activity is necessary for its production in normal humans, and that tonic muscle tone in antigravity leg muscles is responsible for the maintenance of posture. Data reviewed here show that nonreflex, mechanical mechanisms are involved in the maintenance of resting muscle tone; that spinal cord reflex responses are not stereotyped responses, but depend upon the ongoing activity in interneurons upon which inputs from a variety of peripheral sensory receptors and descending fiber systems converge; that long-latency transcortical responses are elicited when a muscle is stretched, and these responses effectively deal with large displacements; and that inertial components and viscoelastic muscle forces can counterbalance small amounts of body sway during quiet standing. In sum, the response to muscle stretch is not fixed and inflexible, but can be adjusted according to the demands of the moment.

Pentylenetetrazol and reflex activity of isolated frog spinal cord.

The superfused in vitro frog spinal cord preparation was used to investigate the effects of pentylenetetrazol (PTZ) on the spinal cord. PTZ depressed monosynaptic, but augmented polysynaptic reflexes, and decreased primary afferent deplorization. Concurrently, in Ringer's solution containing sufficient magnesium or cobalt ions to block synaptic transmission, PTZ antagonized the hyperpolarizing effects on motoneurons and the depolarizing effects on primary afferent fibers of the inhibitory amino acids GABA, beta-alanine, taurine, and glycine. PTZ did not affect responses to the excitatory amino acids glutamic acid and aspartic acid. Furthermore, PTZ did not alter high affinity uptake by cord slices, K+ -evoked release of [3H]GABA from them, or the spinal concentration of GABA. These data suggest that PTZ may produce its excitatory effects by postsynaptic blockade of inhibitory processes mediated by GABA (and possibly by other amino acids).

Phenytoin-induced ophthalmoplegia.

Total external ophthalmoplegia was observed in five patients consequent to the oral or intravenous administration of phenytoin. Coincident with the ophthalmoplegia, the state of consciousness varied from drowsiness to coma and the blood levels of phenytoin ranged from 36 to 55 mug per milliliter. Initially, the eyes were fixed in midposition, and oculocephalic and oculovestibular stimulation failed to evoke either horizontal or vertical eye movements. The return of vestibulo-ocular responsiveness lagged behind the return of consciousness and other reflex activity. The mechanism underlying this ophthalmoplegia may be related to the ability of phenytoin to potentiate inhibitory synapses in the vestibulo-oculomotor pathway which utilize gamma aminobutyric acid, and to increase the discharge rate of Purkinge cells which exert an inhibitory influence on the same structures.

Progression of ventricular wall thickening after liver transplantation for familial amyloidosis.

BACKGROUND: Familial amyloidosis (FAP) is characterized by the progression of neurologic and cardiac impairment ultimately leading to death within 7 to 15 years after the onset of the disease. Liver transplantation represents the only definitive therapy for this disease and has been performed since 1990. METHODS: To determine the effect of liver transplantation on disease progression, electrocardiography and Doppler echocardiography were performed and blindly analyzed on 11 patients with FAP who were followed 0.8 to 8.6 years before liver transplantation and 0.8 to 4.1 years after liver transplantation. RESULTS; After liver transplantation, five patients showed progression of left ventricular wall thickening with increased left ventricular mass, and three of these five showed a reduction in electrocardiographic voltage despite abolition of the mutant protein from the serum. Of the five patients showing progressive wall thickening, four had the transthyretin variant Glu 42 Gly and one patient had the Ala 36 Pro variant; none of the remaining six patients, all of whom possessed the Val 30 Met variant, showed echocardiographic changes. Although 9 of the 11 patients have shown symptomatic improvement in neurologic symptoms, 1 patient has developed heart failure and a second patient has suffered a sudden cardiac death. CONCLUSIONS: After liver transplantation, patients with FAP should have regular clinical evaluations including electrocardiographic and echocardiographic examinations to look for continued deterioration in heart structure or function.

Dorsal root potentials in the isolated frog spinal cord: amino acid neurotransmitters and magnesium ions.

Sucrose gap techniques recorded dorsal root potentials evoked by supramaximal dorsal root stimulation in in vitro, hemisected frog spinal cords. In 0 mM Mg2+ large (mean 13.0 mV), long lasting (mean 8.1 s) dorsal root potentials were recorded which consisted of two components: (1) an early component sensitive to picrotoxin, bicuculline, and low [Cl-]o and presumably produced by activation of GABAA receptors; and (2) a long-duration second component enhanced and lengthened by picrotoxin, bicuculline and low [Cl-]o and thought to result from increased interneuron discharges resulting from depression of GABA-mediated pre- and postsynaptic inhibition. Both the early and late components were reduced by over 90% in amplitude and duration by 20 mM Mg2+ or by kynurenate and bicuculline. The early component of the dorsal root potential may depend mainly upon activation of non-N-methyl-D-aspartate receptors. Thus, the N-methyl-D-aspartate antagonist D-(-)-2-amino-5- phosphonovalerate caused only a modest reduction in the amplitude of the early dorsal root potential component while the non N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione caused a much more substantial reduction. Exposure of the spinal cord to a "physiological" concentration of Mg2+ (1.0 mM) greatly reduced the duration and somewhat reduced the amplitude of the dorsal root potential. The reduction of dorsal root potentials by 1.0 mM Mg2+ appears to be caused by both pre- and postsynaptic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of metabotropic glutamate receptors in the depression of GABA-mediated depolarization of frog primary afferent terminals.

Sucrose gap recordings from the dorsal roots of isolated, hemisected frog spinal cords were used to determine the effects of metabotropic L-glutamate receptor activation on primary afferent terminals by (+/-)-1-amino-trans-1,3-cyclopentane-dicarboxylic acid (t-ACPD). Dorsal root potentials evoked by ventral root volleys were significantly reduced by t-ACPD (30 microM), as were GABA- and muscimol-induced afferent terminal depolarizations. The effects of t-ACPD on GABA-depolarizations depended upon activation of group I metabotropic glutamate receptors, i.e. the effects were blocked by the group I/II antagonist (RS)-alpha-methyl-4-carboxyphenylglycine, but not by the group II antagonist alpha-methyl-(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine or the group III antagonist alpha-methyl-(S)-2-amino-4-phosphonobutyrate and were mimicked by the group I agonist 3,5-dihydroxyphenylglycine but were not mimicked by the group III agonist (S)-2-amino-4-phosphonobutyrate. Increasing the intracellular concentration of 3'-5'-cyclic adenosine monophosphate with 8-bromo-cAMP, forskolin, and 3-isobutyl-1-methylxanthine significantly reduced GABA depolarizations, but the protein kinase inhibitors Rp-adenosine 3,5-cyclic monophosphothioate triethylamine and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide did not alter t-ACPD's depression of GABA depolarizations. The actions of t-ACPD on GABA depolarizations were neither mimicked nor blocked by phorbol-12-myristate 13-acetate, thapsigargin, staurosporine, or arachidonic acid, presumptive indications that the effects of t-ACPD did not involve phosphoinositide hydrolysis, the release of Ca2+ from intracellular stores, or the formation of arachidonate. t-ACPD's effects on GABA depolarizations were blocked by 20 mM Mg2+, the broad spectrum L-glutamate antagonist kynurenate, and the selective N-methyl-D-aspartate antagonist D(-)-2-amino-5-phosphonovaleric acid, but not by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Low concentrations of N-methyl-D-aspartate (10 microM) mimicked the effect of t-ACPD on GABA responses. These results suggest that t-ACPD's depression of GABA depolarizations involves an indirect, three-stage mechanism that includes activation of Group I metabotropic glutamate receptors on interneurons and/or on afferent terminals, the release of L-glutamate from the latter structures, and the activation of N-methyl-D-aspartate receptors on primary afferent terminals. The depression of GABA depolarizations caused by the release of L-glutamate from afferent terminal and/or interneurons leads to a block of presynaptic inhibition (produced in the frog spinal cord by GABA) resulting in a positive feed-forward amplification of reflex transmission.

Changes in membrane potential of frog motoneurons induced by activation of serotonin receptor subtypes.

Application of serotonin to the isolated, hemisected frog spinal cord resulted in two distinctive changes in motoneuron membrane potential: hyperpolarizations were produced by low concentrations (0.01-1.0 microM) and depolarizations by higher concentrations (3.0-100 microM). The hyperpolarizations appeared to be caused by a direct action of the amine upon motoneurons since exposure of spinal cord tetrodotoxin or magnesium ions in concentrations which blocked interneuronal firing and synaptic transmission, respectively did not reduce these responses. In contrast, depolarizations were significantly reduced by tetrodotoxin or magnesium indicating a large indirect component. The use of agonists and antagonists known to discriminate among different subtypes of serotonin receptors indicated that the hyperpolarizations were produced by activation of 5-HT1A receptors and the depolarizations were generated by activation of 5-HT2 and/or 5-HT1C receptors. Accordingly, the selective 5-HT1A agonists 8-hydroxy-2-(n-dipropylamino)tetralin and ipsapirone directly hyperpolarized motoneurons. The changes in potential produced by low concentrations of serotonin and by these agonists were blocked by the 5-HT1A receptor antagonists spiperone and spiroxatrine. In contrast, application of high concentrations of alpha-methyl-5-hydroxytryptamine, a serotonin analog which activates 5-HT1C and 5-HT2 receptor subtypes, depolarized motoneurons. These depolarizations, and those produced by high concentrations of serotonin, were blocked by the 5-HT1C/5-HT2 antagonists ketanserin, methysergide and mianserin. These observations indicate that serotonin can alter the membrane potential of motoneurons directly and indirectly by activation of both 5-HT1 and 5-HT2 receptor subtypes. Activation of different receptor subtypes depends upon the concentration of the amine.

Serotonin1A facilitation of frog motoneuron responses to afferent stimuli and to N-methyl-D-aspartate.

The effects of serotonin and excitatory amino acids on motoneurons were examined by sucrose gap recordings from the ventral root of the isolated, hemisected frog spinal cord superfused with magnesium-free, carbonate-buffered Ringer solution. Low concentrations of serotonin (0.1 microM) and the serotonin1A agonist 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT; 0.01 microM) significantly increased the duration and amplitude of the polysynaptic components of ventral root potentials produced by dorsal root stimulation. The facilitations of the ventral root potentials were blocked by the serotonin1A antagonist spiroxatrine, but were unaffected by the serotonin2 antagonist ketanserin or the serotonin3 antagonist 1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,-dichlorobenzoate (MDL 72222). The actions of 0.1 microM serotonin on motoneuron depolarizations evoked by the putative excitatory amino acid transmitters L-glutamate and L-aspartate were quite variable, but in the presence of ketanserin (20 microM), small consistent increases in amino acid-induced motoneuron depolarizations were observed. 8-OH-DPAT significantly enhanced motoneuron depolarizations elicited by the selective excitatory amino acid agonist N-methyl-D-aspartate in both normal and tetrodotoxin-containing Ringer solution. Quisqualate-induced motoneuron depolarizations were also facilitated by 8-OH-DPAT in normal Ringer solution, but these increases were eliminated by addition of either tetrodotoxin or the N-methyl-D-aspartate antagonist D(-)-2-amino-5-phosphonovalerate to the Ringer superfusate. Kainate-depolarizations were not altered by low concentrations of serotonin or 8-OH-DPAT. Prior exposure of the cord to spiperone, but not ketanserin or MDL 72222 blocked the enhancement of N-methyl-D-aspartate-induced motoneuron depolarizations by 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of cardiovascular adaptations to long-term arm and leg exercise in wheelchair athletes versus long-distance runners.

The effect of long-term arm exercise on cardiac morphology and function is unknown. To study these effects, highly trained wheelchair athletes were compared with long-distance runners and controls. In addition, the wheelchair athletes were compared with the long-distance runners to determine if long-term leg exercise confers a training effect during the performance of dynamic arm exercise. The study included 31 male subjects (mean age of 33+/-5 years), who comprised 3 groups matched for age and weight: wheelchair athletes (n = 9), long-distance runners (n = 12), and healthy controls (n = 10). All underwent echocardiography at rest and arm ergometry exercise testing with expiratory gas analysis. The peak work rate during arm exercise was highest among the wheelchair athletes, and was significantly higher in both groups of trained athletes compared with the control group (p<0.001). Runners demonstrated a significantly lower submaximal heart rate response to arm exercise compared with wheelchair and control subjects. Wheelchair athletes had increased left ventricular (LV) volume and mass by echocardiography compared with controls, but not to the same degree as that of runners. Although chamber dimensions and wall thickness did not differ among the groups, the LV volume index tended to be largest in the runners. Doppler indexes of diastolic LV filling were similar between the trained and untrained subjects. These data demonstrate that both long-term arm and leg exercise yield increases in LV volume and mass compared with untrained control subjects, although to a lesser degree in arm-trained athletes. Runners demonstrated a transfer of training effect in the performance of dynamic arm exercise, as demonstrated by their ability to achieve a higher peak work rate than controls, and showed a lower heart rate response to submaximal exercise than the wheelchair athletes and control subjects.

Effects of dobutamine on Gorlin and continuity equation valve areas and valve resistance in valvular aortic stenosis.

Previous studies demonstrated changes in aortic valve area calculated by the Gorlin equation under conditions of varying transvalvular flow in patients with valvular aortic stenosis (AS). To distinguish between flow-dependence of the Gorlin formula and changes in actual orifice area, the Gorlin valve area and 2 other measures of severity of AS, continuity equation valve area and valve resistance, were calculated under 2 flow conditions in 12 patients with AS. Transvalvular flow rate was varied by administration of dobutamine. During dobutamine infusion, right atrial and left ventricular end-diastolic pressures decreased, left ventricular peak systolic pressure and stroke volume increased, and systolic arterial pressure did not change. Heart rate increased by 19%, cardiac output by 38% and mean aortic valve gradient by 25%. The Gorlin valve area increased in all 12 patients by 0.03 to 0.30 cm2. The average Gorlin valve area increased from 0.67 +/- 0.05 to 0.79 +/- 0.06 cm2 (p < 0.001). In contrast, the continuity equation valve area (calculated in a subset of 6 patients) and valve resistance did not change with dobutamine. The data support the conclusion that flow-dependence of the Gorlin aortic valve area, rather than an increase in actual orifice area, is responsible for the finding that greater valve areas are calculated at greater transvalvular flow rates. Valve resistance is a less flow-dependent means of assessing severity of AS.

Pulmonary arterial thrombosis in secundum atrial septal defect.

Nineteen adolescent or adult patients with secundum atrial septal defect (ASD) underwent pulmonary arteriography to evaluate the presence of proximal pulmonary arterial (PA) thrombosis. This procedure demonstrated proximal PA thrombosis in 8 patients (group 2). These patients had a distinctive hemodynamic profile, consisting primarily of significant PA hypertension. None of the 11 patients with normal angiograms (group 1) had severe PA hypertension (p less than 0.0001). Proximal PA thrombosis appears to be the major factor in the development and progression of PA hypertension in adult patients with ostium secundum ASD. Pulmonary angiography should be undertaken in all adult patients with ostium secundum ASD who have at least moderate PA hypertension. Long-term anticoagulation is advocated for patients with PA thrombosis irrespective of a decision for surgical intervention.

Comparison of the usefulness of Doppler pressure half-time in mitral stenosis in patients < 65 and > or = 65 years of age.

Doppler pressure half-time is a reliable method for estimating mitral valve area when net left atrial and ventricular compliance remain stable. The accuracy of Doppler pressure half-time in estimating mitral valve area in older patients is unknown. We studied 80 patients (65 women and 15 men, aged 56 +/- 14 years) with cardiac catheterization and echocardiography. Mitral valve area was calculated using the Gorlin formula and by the Doppler pressure half-time method. Patients were stratified into those aged < 65 years (n = 57), and those aged > or = 65 years (n = 23). The discordance between pressure half-time and Gorlin-derived mitral valve area was assessed and related to multiple clinical, echocardiographic, and hemodynamic variables. The difference between pressure half-time and Gorlin-derived mitral valve area was greater in the older than in the younger patient (0.34 +/- 0.30 vs 0.15 +/- 0.27 cm2, p = 0.009) but the older group had smaller mitral valve areas by the Gorlin method (0.72 +/- 0.18 vs 0.89 +/- 0.32 cm2, p = 0.02) and lower cardiac output. The difference between pressure half-time and Gorlin remained greater in the group of older patients (0.32 +/- 0.30 vs 0.19 +/- 0.22 cm2, p = 0.04), even when the analysis was restricted to patients with similar mitral valve area (< 1 cm2 by the Gorlin method). Using multivariate analysis, age > or = 65 years remained the only significant predictor of the discrepancy between pressure half-time and Gorlin mitral valve area. Thus, when compared with Gorlin-derived mitral valve area, pressure half-time overestimated valve area in older patients, and this technique for estimating mitral valve area should be used with caution in patients > or = 65 years of age.