Left ventricular volume changes during supine exercise in young endurance athletes.

AIM: The primary objective of the study was to measure the relative left ventricular volumes and the changes in left ventricular ejection fraction during supine position from rest to exercise in young endurance athletes. The secondary objective was to examine if there were gender differences regarding the volume reply and ejection fraction with exercise. METHOD: Sixty-five (35 female and 30 males) young healthy Swedish orienteers participated in the study. Left ventricular volume and ejection fraction changes between rest and submaximal supine bicycle exercise were measured with radionuclide ventriculography. RESULTS: The mean left ventricular end-diastolic volume increased by 13% (P < 0.001) but there was no change in end-systolic volume. Stroke volume was found to increase by 21% (P < 0.001). Left ventricular ejection fraction increased significantly (>0.04 units) in 54% of the athletes from rest to exercise; 5% of the athletes showed a decrease in ejection fraction. A negative correlation was found between ejection fraction at rest and the difference in ejection fraction from rest to exercise (r = -0.38, P = 0.002). There were no gender differences in the left ventricular volume changes or ejection fraction. CONCLUSION: During submaximal supine exercise, the adjustments in cardiac volumes in endurance athletes were small. There were no gender disparities concerning the left ventricular volume reply during exercise.

Wall motion abnormalities in male elite orienteers are aggravated by exercise.

During the period 1979-92, 16 (15 men and one woman) sudden unexpected cardiac deaths occurred among young Swedish orienteers. This finding indicated a sharp increase in the death rate of orienteers, and necropsy demonstrated that myocarditis was a common histopathological finding. Therefore, an extensive non-invasive cardiac investigation was performed. A total of 59 male élite orienteers (mean age 23 years) and 36 cross-country skiers and middle-distance runners (mean age 22 years), serving as controls, were examined by both echocardiography at rest and radionuclide ventriculography at rest and during exercise. Wall motion abnormalities were found in eight orienteers using echocardiography. The purpose of this study was to examine whether the group of orienteers with wall motion abnormalities found using echocardiography had a smaller increase in ejection fraction from rest to exercise using radionuclide ventriculography than the rest of the orienteers and the controls, indicating an aggravation of the wall motion abnormalities during exercise. There were no significant differences in the ejection fraction at rest between the groups. In the orienteers with wall motion abnormalities (group 1), 62% (five out of eight) had less than a 0.05 unit increase in left ventricular ejection fraction compared with 27% (14 out of 51) of the remaining orienteers (group 2) and 19% (7 out of 36) of the controls (group 3). A comparison of athletes in group 1 with those in groups 2 and 3 combined revealed a statistically significant difference (P < 0.05). The divergent response in left ventricular ejection fraction during exercise suggests an aggravation of the wall motion abnormalities with exercise. Both the echocardiographic and the radionuclide ventriculographic findings indicate that the orienteers in group 1 had concealed left ventricular damage.

Distribution patterns of ventricular premature complexes in long-term electrocardiographic recordings and their usefulness in disclosing modulated parasystole.

Long-term electrocardiographic recordings from 25 patients with abundant ventricular premature complexes (VPCs) were screened with a computer program for sequences of interectopic intervals with the number of sinus beats consistent with manifest or concealed bigeminy/trigeminy. On average, 19.0% of VPCs in this patient series were followed by an uninterrupted sequence of greater than or equal to 10 interectopic intervals with concealed bigeminy. The corresponding figure for concealed trigeminy was 2.2%, for manifest bigeminy 9.6%, and for manifest trigeminy 0.8%. The longest sequence with concealed bigeminy comprised 149 interectopic intervals. The corresponding figure for concealed trigeminy was 135 interectopic intervals. The sequences of concealed bigeminy occurred at significantly lower heart rates than those of concealed trigeminy. These findings can be explained by the entrainment phenomena described in experimental models of modulation of a ventricular parasystolic focus across a zone of impaired conduction.

Deduction of triphasic phase response curves from ventricular parasystole.

Modulation of ventricular parasystole by sinus beats has been shown to result in a biphasic phase response curve. Some reports also indicate that the modulation effect could be described by a triphasic response with an early phase of acceleration, which would correspond to the supernormal phase of excitability. Two cases of such triphasic phase response curves are reported. The coexistence of ventricular couplets and parasystole is also discussed. The second beat of the couplet has often been explained by reentry or reflection, but could also be interpreted as due to supernormal modulation, resulting in an accelerated second ectopic response.

Deduction of biphasic phase response curves from ventricular parasystole.

The mechanisms behind ventricular premature beats may be divided into two main categories, reentry and modulated parasystole. Although it is relatively easy to distinguish among arrhythmia generating mechanisms on the cellular level, it is far more difficult in the clinic. Modulation of ventricular parasystole by sinus beats has been shown to result in a biphasic phase response curve. Two cases are reported where the deduction of such phase response curves from long-term ECG recordings is discussed and described as a stepwise procedure.

Distribution patterns of ventricular premature complexes at different heart rates.

The relation between distribution patterns of ventricular premature complexes (VPCs) and heart rate in Holter recordings abundant in VPCs was analyzed using computer-assisted determination of the number of interectopic sinus beats at different heart rates. Within the complete 24-hour heart rate spectrum, zones were demonstrated that were characterized by manifest or concealed bigeminy or manifest or concealed trigeminy. Bigeminy zones were found in 26 and trigeminy zones in 21 of 42 patients. Bigeminy zones were found at a significantly lower heart rate, on the average, then trigeminy zones. In 10 patients both bigeminy and trigeminy zones were observed. Bigeminy and trigeminy zones probably correspond to the distribution patterns of VPCs predicted from modulation of a pacemaker and reflected reentry, both of which can be induced by electrotonically mediated impulses across a zone of impaired conduction in isolated bundles of Purkinje fibers. The bigeminy and trigeminy zones will correspond at least partly to the entrainment zones found during electrotonic modulation of parasystolic foci. The bigeminy zones will correspond to 2:1 entrainment and the trigeminy zones mainly to 3:1 entrainment.

Ovarian function, bleeding control and serum lipoproteins in women using contraceptive vaginal rings releasing five different progestins.

Ovarian function, bleeding patterns and serum lipoproteins were studied in women using contraceptive vaginal rings (CVRs) of dimethyl-polysiloxane impregnated with steroids. The different CVRs were used for about 10 cycles each. The following groups were studied, with the daily steroid dosage given in parentheses. Women using CVRs delivering levonorgestrel (290 micrograms), norethisterone (850 micrograms), medroxyprogesterone acetate (700 micrograms) or megestrol acetate (1.9 mg), all of which were in combination with estradiol (200 ug). Women using CVRs delivering progesterone (5.2 mg). Women taking megestrol acetate orally (15 mg/day) for three weeks. In all women except those using the levonorgestrel CVR, there were indications of incomplete suppression of ovarian activity as shown by elevated levels of progesterone and/or estradiol peaks. Bleeding control seemed to be good with the levonorgestrel CVR and rather poor with the others. Levonorgestrel treatment was associated with a decrease in high density lipoprotein cholesterol (32%) and triglycerides (25%) and a 16% decrease in apolipoprotein A-I. Norethisterone induced a 10% decrease in A-I and a reduction of cholesterol in very low density lipoprotein. All other lipid and apolipoprotein B, A-I and A-II values were unaltered with the administration of the CVRs and with oral megestrol acetate. Levonorgestrel was given in a higher dose than the other progestins, but the absence of effects of the high oral dose of megestrol acetate on the serum lipoproteins indicates that the progesterone-derived progestins in adequate doses probably would not alter the lipoprotein metabolism. Higher doses of progestins are needed to achieve acceptable control of ovarian activity and bleeding patterns than seen with these CVRs.

Effects of contraceptive vaginal ring treatment on vaginal bacteriology and cytology.

The presence of aerobic and anaerobic bacteria, yeasts and mycoplasma/ureaplasma was investigated in seventeen women before and after six months use of a contraceptive vaginal ring releasing levo-Norgestrel and estradiol and in 16 women using an oral contraceptive containing levo-Norgestrel and ethinylestradiol. Apart from an increase in yeasts in both groups, no significant changes in the vaginal bacteriology could be found. Vaginal smears were examined before and during treatment for up to two years in a group of 120 women participating in a clinical trial of the contraceptive vaginal ring. No changes in the squamous epithelium or cylinder cells were found. The amount of leucocytes increased in the smears. The results indicate that use of the contraceptive vaginal ring does not affect the bacterial ecology of the vagina. The increase in leucocytes indicates a weak inflammatory reaction which might explain the increase in vaginal discharge often observed by women using the contraceptive vaginal ring.

Serum lipoprotein and apolipoprotein changes during treatment with a contraceptive vaginal ring containing levonorgestrel and estradiol.

Contraceptive vaginal rings containing estradiol and levonorgestrel were used by 22 women during 219 cycles. The estrogenicity was low and the daily dose of levonorgestrel was about 290 micrograms. The triglyceride and cholesterol concentrations decreased in whole serum and, to varying degrees, in the different lipoprotein classes. The most consistent change was a 25% (p less than 0.001) reduction in the cholesterol content of the high-density lipoprotein (HDL) fraction. The cholesterol concentration in low-density lipoprotein decreased by 11% after the first 3 months, but increased during the ensuing 9 months of treatment to regain pretreatment level. Percentage-wise, the apolipoprotein B and A-I concentrations, determined by rocket immunoelectrophoresis, were less affected than the LDL- and HDL-cholesterol concentrations. The composition of the LDL and HDL particles seemed thus to alter during the treatment. The pronounced effect on the HDL levels seen is consistent with earlier findings of a dose-dependent, androgenic effect of gestagens derived from 19-nortestosterone. However, the low basal level of LDL and its further decrement during treatment alleviate the supposedly unfavorable effect of HDL reduction from the atherogenic point of view.

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. I-Use effectiveness. An international comparative trial.

PIP: Contraceptive vaginal rings (CVRs), with approximate daily release rates of 250-290 mcg of levonorgestrel and 150-180 mcg of estradiol and manufactured in a shell design, were studied for effectiveness and acceptability in multicentered trials involving 1103 ring users in Brazil, Chile, Dominican Republic, Sweden, U.S., Denmark/Finland, and Nigeria. A comparison group of 533 women used the oral contraceptive Nordette. Both 1st and all segment 1 year gross pregnancy rates among CVR users were less than 3/100, rates similar to Nordette users. Continuation at 1 year was 50/100 users of the ring (all segments) and 38/100 among Nordette users, more of whom were lost to follow-up. Gross 1 year rates of termination for medical reasons ranged from 25-29/100. Ring users were more likely to terminate for vaginal problems and pill users for headache, nausea, and associated reasons. These trials indicate that CVRs of this design are as effective and have continuation rates equal to and possibly superior to Nordette under the same study conditions.^ieng

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. II-Subjective and objective measures of effects. An international comparative trial.

Comparative clinical trials of 2 sizes of contraceptive vaginal rings and of an oral contraceptive were undertaken at 8 investigational sites (9 clinics). More than 500 women enrolled on each of the 3 study regimens. Side effects of the rings and of Nordette, the oral contraceptive, were evaluated by noting spontaneous complaints, by recording medications taken and by physical examination. Inquiries about changes in the frequency of specific conditions were made at the end of the subjects participation in the first year of the study. The incidence of spontaneous complaints was similar among users of the 2 different-sized rings and of the pill.

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. III-Menstrual patterns. An international comparative trial.

Menstrual events among users of contraceptive vaginal rings (CVRs), releasing levonorgestrel and estradiol, were studied in comparison with a combined oral contraceptive, Nordette, in multicentered trials. CVRs were made with outside diameters of 50 and 58 mm and released about 250 micrograms and 290 microgram of levonorgestrel and 150 microgram and 180 microgram of estradiol per day, respectively. The CVRs were used continuously for 3 weeks and then removed for 1 week. Both the CVRs and Nordette were perceived to reduce menstrual flow and days of menstrual bleeding. Twenty to 25% of CVR users perceived increased intermenstrual bleeding or spotting. Diaries indicate, however, that on average, CVR users experienced about 1 day per month of bleeding or spotting with the ring in place. CVRs and Nordette produced approximately the same total number of bleeding and spotting days during 6 cycles of use, 27-29, but the small (50-mm OD) ring was associated with somewhat more spotting. This ring was also associated with somewhat more prolonged bleeding and spotting runs and with more prolonged nonbleeding intervals than reported by users of the larger (58-mm OD) ring or of Nordette. Differences among regimens, however, tended to be small even when statistically significant. Evidence from menstrual diaries indicates that these CVRs, and in particular 58-mm ring, provide control over the menstrual cycle comparable to the Nordette.

Comparison of the metabolic effects of two hormonal contraceptive methods: an oral formulation and a vaginal ring. I. Carbohydrate metabolism and liver function.

A prospective, long-term study was undertaken to compare the metabolic effects of a contraceptive vaginal ring releasing levonorgestrel (about 290 microgram per day) and estradiol (about 180 microgram per day) and a combined oral contraceptive containing 30 microgram ethinylestradiol and 150 microgram levonorgestrel in two groups of women (n = 22 and 20, respectively). An intravenous glucose tolerance test, including determination of the insulin response to glucose, and liver function tests were performed. Both the glucose tolerance and fasting values of glucose were unaltered. The early insulin response to glucose increased by 50 percent in the contraceptive ring roup after one year of treatment, but not in the oral contraceptive group. All other insulin values were unchanged. All liver function values remained within the normal range in all subjects. There was a small significant decrease in alkaline phosphatases in both groups, which is in contrast to the effects of the early combined pills, which could cause an elevation. It is concluded that neither of these two contraceptive methods, the effects of which are predominantly gestagenic, seems to cause impairment of glucose tolerance or hepatic function.

Comparison of the metabolic effects of two hormonal contraceptive methods: an oral formulation and a vaginal ring. II. Serum lipoproteins and apolipoproteins.

In a long-term, prospective study the effects on lipoprotein lipids and apolipoproteins (apo) of a combined oral contraceptive (OC) (30 micro gram ethinylestradiol and 150 micro gram levonorgestrel) and a contraceptive vaginal ring (CVR) releasing estradiol (about 180 micro gram per day) and levonorgestrel (about 290 micro gram per day) were compared. The two treatments induced significantly different effects. In the OC group the lipoprotein-lipid concentrations showed only minor changes, but apolipoproteins (apo) B and A-I increased by about 15%. In contrast, during treatment with the CVR there was a 25% decrement of cholesterol in high density lipoprotein (HDL) and at most 10% in low density lipoprotein (LDL) cholesterol, with only minor effects on apo B and A-I. The ratio of LDL and HDL cholesterol increased in the CVR group but not in the OC group. The results also indicate a change in the composition of the LDL and HDL particles, with an altered lipid/protein ratio, during both contraceptive treatments. Despite the impressive relative increase in LDL:HDL ratio in the contraceptive ring group, the average absolute value of this ratio did not reach the mena for healthy men.

Slow evoked cortical responses to linear frequency ramps in subjects with cochlear lesions.

Slow evoked cortical potentials in response to linear frequency ramps of a continuous pure tone with a 1 kHz base frequency have been recorded from ten relatively young subjects with hearing loss of cochlear origin. At small frequency ramps, the N1-latency of their responses to the three ramp durations studied (20, 100, 500 msec) was significantly longer than those of a group with normal hearing. As the ramps are made larger, the difference between the latencies of the pathological group and the normal group becomes smaller; above a certain rate of frequency change, the latency of N1 becomes smaller in the pathological cases than in the normal group. This crossover occurs at frequency change rates around 1-3 kHz/sec. It is concluded that recording of evoked cortical responses to frequency ramps may provide an additional tool in the differential diagnosis of hearing disorders.

Discrimination of frequency ramps in subjects with cochlear hearing loss.

The auditory sensitivity for detecting linear frequency sweeps of a continuous pure tone has been studied in ten young subjects with cochlear hearing loss. The mean thresholds were elevated by a factor of 2.8 as compared with a normal group over the whole range of ramp durations studied (10-500 msec). The results show that this elevation is most likely caused mainly by the cochlear lesion per se, other possible factors having only a minor effect. No clear correlations could be found between thresholds for frequency change and results of other pure tone audiometric tests. Such tests thus cannot predict a subject's frequency discrimination.

Thresholds for linear frequency ramps of a continuous pure tone.

The human auditory sensitivity in detecting linear frequency ramps of a continuous pure tone has been studied. It is shown that for short ramp durations (less than 200 msec) discrimination depends on the difference between base and plateau frequencies, the mean threshold being about 3 Hz at 1 kHz. For longer ramp durations (greater than 200 msec), discrimination was found to be based on detection of the actual frequency sweep. No significant difference was found between thresholds for upward and downward sweeps. Expressed in Hz, the threshold for frequency change was approximately constant for base frequencies up to 1 kHz, above which it increased, reaching approximately 14 Hz at 4 kHz. There was no significant difference in the threshold for frequency change from 40 to 80 dB HL but at 20 dB HL the threshold was significantly higher than at 40 dB HL. Intra-individual variation in thresholds was found to be smaller than inter-individual variation. The results are discussed in relation to previous frequency discrimination data, where either tone pulse pairs, continuous frequency modulation or frequency ramps were used as stimuli.

Slow evoked cortical responses to linear frequency ramps of a continuous pure tone.

Slow evoked cortical potentials from ten young normal-hearing subjects have been recorded as responses to linear frequency ramps of a continuous pure tone. Frequency changes from 10 to 500 Hz were studied; the rate of frequency change was varied from 0.02 to 50 kHz/s while the duration of the change was varied from 10 to 500 ms. The rate of frequency change was shown to have the greatest bearing on the responses except for frequency ramp durations below 50 ms and frequency changes below 50 Hz. The base frequencies (250-4000 Hz) and sound levels (20-80 dB HL) exerted an influence on the evoked responses that was qualitatively similar to their influence on behavioral thresholds. The direction of the frequency sweep had no significant influence on the evoked responses. A functional model is proposed in which the time derivate of the signal frequency is integrated with an adaptable integration time that is controlled by the rate of the frequency change.