Electrocardiographic manifestations in female team handball players: analyzing ECG changes in athletes.

Introduction: Long-term intense training leads to structural, functional, and electrical remodeling of the heart. How different sports affect the heart has not been fully investigated, particularly for female athletes. The aim of the present study was to investigate the morphology of 12-lead resting electrocardiogram (ECG) in elite female handball players compared to non-athlete female subjects. Potential changes will be explored to see if they could be explained by differences in cardiac dimensions and exercise hours. Materials and methods: A cross-sectional study of 33 elite female team handball players compared to 33 sex and age-matched, non-athletic controls (age range 18-26 years) was performed. All participants underwent a resting 12-lead ECG and an echocardiographic examination. ECG variables for left ventricular hypertrophy and durations were evaluated and adjusted for cardiac dimensions and exercise hours using ANCOVA analysis. A linear regression analysis was used to describe relation between echocardiographic and ECG measures and exercise hours. Results: The female handball players had larger cardiac dimensions and significantly lower heart rate and QTc duration (Bazett's formula) as well as increased QRS and QT durations compared to controls. The 12-lead sum of voltage and the 12-lead sum of voltage ∗ QRS were significantly higher among handball players. Changes in ECG variables reflecting the left ventricle could in part be explained by left ventricular size and exercise hours. Correlation with exercise hours were moderately strong in most of the echocardiographic measures reflecting left ventricular (LV), left ventricular mass (LVM), left atrium (LA) and right atrium (RA) size. Poor to fair correlations were seen in the majority of ECG measures. Conclusions: Female team handball players had altered ECGs, longer QRS and QT durations, higher 12-lead sum of voltage and 12-lead sum of voltage ∗ QRS as well as shorter QTc (Bazett's formula) duration compared to non-athletic controls. These findings could only partly be explained by differences in left ventricular size. Despite larger atrial size in the athletes, no differences in P-wave amplitude and duration were found on ECG. This suggest that both structural, and to some degree electrical remodeling, occur in the female team handball players' heart and highlight that a normal ECG does not rule out structural adaptations. The present study adds knowledge to the field of sports cardiology regarding how the heart in female team handball players adapts to this type of sport.

Cardiac dimensions and function in female handball players.

AIM: Long-term intensive endurance training leads to increased left ventricular mass and increased left ventricular end-diastolic and left atrial end-systolic diameters. Different types of sports tend to give rise to distinct morphological forms of the athlete's heart. However, the sport-specific aspects have not been fully investigated in female athletes. The purpose of the present study was to investigate differences in left and right cardiac dimensions, cardiac volumes, and systolic and diastolic function in elite female handball players compared to sedentary controls. METHODS: A cross-sectional study of 33 elite female handball players was compared to 33 matched sedentary controls. Mean age was 21.5±2 years. The subjects underwent echocardiography examinations, both 2-dimensional (2DE) and 3-dimensional (3DE). Cardiac dimensions and volumes were quantified using M-mode, 2DE and 3DE. Systolic and diastolic left ventricular functions were also evaluated. All cardiac dimensions and volumes were adjusted for body surface area (BSA). RESULTS: Left atrium and left ventricle volumes were significantly (P<0.001) larger in elite female handball players compared with sedentary controls. Even right atrium area as well as right ventricular end-diastolic and end-systolic area were significantly (P<0.001) larger in elite female handball players. Significant differences were observed in three out of five systolic parameters. Most diastolic function parameters did not differ between the two groups. CONCLUSION: The findings from the present study suggest that similar cardiac remodeling takes place in elite female handball players as it does in athletes pursuing endurance or team game sports.

The effect of cromakalim on the electrical properties of and [86Rb+] efflux from normal and hypertrophied rat bladder.

1. The activity of smooth muscle strips from normal and hypertrophied rat bladders was compared. The hypertrophied bladders were produced by partially obstructing the urethra 8-13 weeks previously. 2. Spontaneous mechanical activity was more frequent and smaller in amplitude in strips from normal than hypertrophied bladders and was less sensitive to cromakalim, being reversibly abolished by cromakalim at 10(-6) mol/L compared with 10(-7) mol/lL for hypertrophied bladder. 3. The mean resting membrane potentials of smooth muscle cells from normal and hypertrophied rat bladders were -47.2 and -47.6 mV, respectively. Bursts of spontaneous action potentials, corresponding to the mechanical activity, were seen in some cells. 4. Nifedipine at 10(-6) mol/L had no significant effect on the resting membrane potential. Occasional single spikes occurred with increased duration and the after hyperpolarization was abolished. Cromakalim at 10(-5) mol/L produced hyperpolarization of 3-9 mV and, in the continued presence of the drug, occasional singe spikes could be recorded from both normal and hypertrophied bladders. 5. Nifedipine at 10(-6) mol/L abolished movement but did not significantly alter [86Rb+] efflux from strips from either normal or hypertrophied bladders. Addition of cromakalim at 5 x 10(-6) or 5 x 10(-5) mol/L in the presence or absence of nifedipine increased efflux from the normal bladder by 30-40%. In the hypertrophied bladder the efflux increased by about 14% and 28% in the presence of 5 x 10(-6) and 5 x 10(-5) mol/L cromakalim, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of unilateral pelvic ganglionectomy on urinary bladder function in the male rat.

Micturition interval and micturition volume were measured in water loaded male rats before and up to 6 weeks after unilateral pelvic ganglionectomy. There was no effect on micturition interval until 7 days after the ganglionectomy. Micturition interval then remained increased. Maximal micturition volume was higher than in the control group from 4 to 14 days after surgery. Cystometrograms were recorded 12 days or 6 weeks after surgery. At 12 days the micturition pressure was lower in the unilaterally ganglionectomized than in the controls. After 6 weeks there was no significant difference in micturition pressure. A reduction of micturition pressure by about 50% was observed after i.v. injection of atropine, but no residual urine developed. Electron microscope investigation showed a considerable decrease in number of nerve terminals on the ganglionectomized side 3 days after surgery. Most of them were devoid of synaptic vesicles. On the contralateral side the majority of nerve terminals appeared normal, but many had a decreased number of vesicles. After 14 days the number of terminals was still lower than normal on the ganglionectomized side. They generally contained only a small number of vesicles. Also, on the contralateral side some nerve endings with the reduced complement of vesicles were found. We suggest that the effects of unilateral ganglionectomy on micturition volume and interval can be explained by a decreased sensory input from the bladder and that the effect on micturition pressure is due to a transient decrease in number and function of motor nerve terminals in the detrusor muscle.

Urinary bladder function in rats with hereditary diabetes insipidus; a cystometrical and in vitro evaluation.

Bladder function was investigated in female rats with hereditary diabetes insipidus (DI) and in healthy controls, in vivo by means of recordings of micturition pattern and cystometry, and in vitro in organ bath experiments. Rats with DI exhibited bladder hypertrophy, the weight of the bladder in these rats being two times that of controls. Recordings of micturition pattern showed that DI-rats had an increased 24 hour diuresis and micturition volume, and decreased micturition interval in comparison with controls. Cystometry recordings revealed increased bladder capacity and micturition volume in DI-rats. However, in these rats basal bladder pressure and threshold pressure were lower than in controls. No significant changes in micturition pressure or bladder compliance were observed, and none of the rats had residual urine. In organ bath studies, a lower maximal response to electrical field stimulation was obtained in bladder strips from DI-rats, than in the control strips, when expressed relative to the response elicited by K(+)-solution. When activated by field stimulation, the DI-bladder strips and the control strips had similar sensitivity to muscarinic receptor blockade with scopolamine at all stimulation frequencies. The sensitivity to carbachol was similar in the two groups. The results suggest that the increased functional demands of DI on the detrusor do not result in major changes pre- or postjunctionally. Further, several of the previously reported urinary bladder changes observed in rats with diabetes mellitus (DM) are similar to those now reported in rats with DI, emphasizing the importance of an increased diuresis per se for the development of alterations in bladder function. However, in contrast to the findings in DM rats, the sensitivity to electrical stimulation of nerves during blockade of muscarinic receptors was similar in DI-rats and their controls. This supports our previous suggestion that the increased resistance to muscarinic receptor blockade of the bladder in DM-rats at low stimulation frequencies is induced by the disease (diabetes mellitus) as such and not by the increased diuresis.

Effects of age and streptozotocin-induced diabetes on contents and effects of substance P and vasoactive intestinal polypeptide in the lower urinary tract of the rat.

The urinary bladder and urethral content of substance P and vasoactive intestinal polypeptide and the in vitro effects of the peptides on the bladder were studied at 6 weeks and 6 months of streptozotocin-induced diabetes in the rat. The results were compared with those obtained in age-matched control animals. Both short-term and long-term streptozotocin treatment induced a clearcut increase in bladder weight. Bladder substance P content was increased in both groups of diabetic animals but substance P concentration was similar in control and diabetic animals. Vasoactive intestinal polypeptide content was slightly higher in diabetic animals than in controls but vasoactive intestinal polypeptide concentration was significantly lower in the bladders from both short-term and long-term diabetic animals. The bladder contractile response to substance P was similar in all groups of animals and vasoactive intestinal polypeptide was found to be devoid of contractile or relaxatory effects in the rat bladder. No change in urethral weight was seen with diabetes. There were no clear-cut changes in the urethral contents or concentrations of substance P and vasoactive intestinal polypeptide. The study also enabled comparisons between younger (3 months) and older (9 months) rats. This comparison showed a decrease in the concentrations and contents of substance P and vasoactive intestinal polypeptide between young and older rats. The changes were seen in both the bladder and the urethra and were similar in diabetic and normal animals.

Functional responses of different muscle types of the female rat urethra in vitro.

The influence of muscle type on functional responses of the female rat urethra was investigated using morphological and functional in-vitro techniques. The urethral submucosa was found to contain longitudinally or obliquely oriented smooth muscle cells. The muscularis layer is composed of circularly oriented muscle cells. Near the bladder orifice smooth muscle fibres dominate, but in the mid-urethra the vast majority is circularly oriented striated muscle cells. Circular preparations responded to electrical field stimulation in vitro with a rapid contraction. Stimulation with single impulses resulted in a twitch response; frequencies exceeding 5-10 Hz induced a summation and tetanus. The response was unaffected by phenoxybenzamine, propranolol and scopolamine and had a low sensitivity to calcium-free solution but was sensitive to suxamethonium and tetrodotoxin. Using longer impulse trains stimulation evoked also a slow contraction, sensitive to calcium-free solution. In longitudinal preparations stimulation induced a relaxation followed by a contraction, responses much smaller than those seen in the circular preparations. Both preparations relaxed on addition of calcitonin gene-related peptide or capsaicin. The relaxation to calcitonin gene-related peptide was larger than that to capsaicin in longitudinal preparations but equally large in the circular ones. Substance P and 5-hydroxytryptamine contracted both preparations. The longitudinal urethra showed a larger contraction to 5-hydroxytryptamine than to substance P, whereas both substances induced similar responses in the circular preparations. The study shows a similar muscle arrangement in the female rat urethra as described in humans and further points to a functional differentiation between the different types of muscle.

On the reversibility of functional bladder changes induced by infravesical outflow obstruction in the rat.

Rats were subjected to infravesical outflow obstruction for six weeks. The bladder function was followed by cytometrical and in vitro investigations and by recordings of micturition pattern before and after removal of the obstruction. Cytometrical investigations showed that outflow obstruction for six weeks induced a bladder instability. Further, in the presence of obstruction the micturition pressure was large as was the bladder capacity and the rats had residual urine. After removal of the obstruction the bladder function rapidly normalized. The bladder instability disappeared within one week, bladder capacity decreased as did the micturition pressure. Moreover, only a minor amount of residual urine was present post-obstruction. In vitro investigation showed that the response to carbachol and to electrical stimulation was similar in normal and obstructed bladders. However, after removal of the obstruction a supersensitivity to carbachol as well as to electrical stimulation had developed. Obstructed bladders showed a markedly decreased response to substance P. The sensitivity to substance P was rapidly enhanced post-obstruction and after four days the response was restored to the control level. The present study shows that the bladder function in rats with infravesical outflow obstruction rapidly normalized after removal of the obstruction. The disappearance of the bladder instability despite the developed supersensitivity to muscarinic receptor stimulation supports the opinion that the bladder instability is not of muscarinic origin.

Effects of cromakalim (BRL 34915) and pinacidil on normal and hypertrophied rat detrusor in vitro.

Normal and hypertrophied rat detrusor were investigated in vitro with regard to effects of the K(+)-channel openers pinacidil and cromakalim. Both drugs abolished spontaneous contractile activity and induced a relaxation of normal and hypertrophied detrusor preparations. In both types of preparation, contractions elicited by K+, carbachol or electrical field stimulation were depressed in the presence of the K(+)-channel openers. Responses induced by K+ or electrical stimulation were more reduced in the hypertrophied than in the normal detrusor. Both K(+)-channel openers increased the efflux of 86Rb+ in a concentration-dependent way and this increase was similar in normal and hypertrophied detrusor. If applicable to man, this data suggest that K(+)-channel openers may be effective in the treatment of bladder instability secondary to outflow obstruction.

Muscarinic supersensitivity in the rat urinary bladder after capsaicin pretreatment.

The effects of capsaicin on urinary bladder function have been investigated in adult rats. Ten days after capsaicin treatment immunocytochemical investigations showed a nearly complete disappearance of substance P (SP) and calcitonin gene-related peptide (CGRP) in all parts of the bladder. Recordings of micturition patterns and cytometrical investigations in conscious animals revealed no functional effects of capsaicin treatment. In-vitro experiments showed that the contractile response to substance P was similar before and after capsaicin treatment and CGRP exerted no contractile effects on the urinary bladder in either group of rats. The concentration-response curve to carbachol as well as the frequency-response curve to electrical stimulation were significantly shifted to the left in bladder muscle after capsaicin treatment. However, the maximal responses were similar in control and capsaicin-treated bladders. In the presence of scopolamine the maximal response to electrical stimulation was clearly lower in bladders subjected to capsaicin treatment than in controls. In conclusion, depletion of substance P and CGRP in the rat urinary bladder by capsaicin induced no supersensitivity to these peptides. However, the increased sensitivity to carbachol and to electrical stimulation seen after capsaicin treatment indicates the development of a supersensitivity to muscarinic receptor stimulation. Despite this supersensitivity in vitro no functional effects of capsaicin treatment were found in vivo.

Effects of variations in extracellular pH on spontaneous contractile activity and response to nerve stimulation in smooth muscle from rat urinary bladder.

The effects of variations in extracellular pH have been studied on rat detrusor muscle in vitro. At pH 7.4 a continuous low amplitude spontaneous contractile activity was found. At pH 6.75 the contractions became more regular with periods of relaxation between the contractions which had increased in amplitude. At pH 7.85 the reverse was found. The results are interpreted as a membrane effect of pH. No effect of pH on amplitudes of high-K(+)-induced contractures was found. Carbachol dose-response relations and maximal contraction amplitude to carbachol was similar at pH 7.4 and 6.75. A significant depression in response to nerve stimulation was, however, noted at pH 6.75. We suggest that, while the force output of the activated detrusor smooth muscle cell is unaffected by changes in extracellular pH, a prejunctional inhibition of nerve induced contraction might occur at low pH.

Bladder function in rats with short- and long-term diabetes; effects of age and muscarinic blockade.

The development of alterations in urinary bladder function was studied in rats during six months of streptozotocin-induced diabetes. The results were compared with those obtained in age-matched controls. The bladders from the control rats developed with increasing age an increased micturition volume, a decreased micturition interval, and increased bladder compliance and capacity despite an unaltered bladder weight and unaltered passive and active length-tension relations. The effects of muscarinic blockade were somewhat more pronounced in the older control rats. Following streptozotocin 24 hour diuresis increased rapidly to stabilize within two weeks at a level 15 times higher than the original. This was accomplished initially by an increase in the micturition frequency and then gradually by an increased micturition volume. After six weeks bladder weight had increased more than twofold and did not increase further with time. Despite this both micturition volume and bladder capacity increased from six weeks to six months of diabetes. The diabetic bladders had at low frequencies of stimulation a higher resistance to scopolamine than their age-matched controls. At higher frequencies the resistance to muscarinic blockade showed a similar decrease with age as for the controls. The more pronounced decrease in micturition pressure following atropine treatment in six weeks diabetic rats thus suggests an increased excitation frequency during micturition. No supersensitivity to carbachol was found even after six months of diabetes.

Effects of pinacidil and cromakalim (BRL 34915) on bladder function in rats with detrusor instability.

Normal rats as well as rats with bladder hypertrophy secondary to outflow obstruction were investigated cystometrically before and after administration of the potassium channel openers pinacidil or cromakalim one mg./kg. orally. In normal rats cromakalim decreased micturition pressure by 15 +/- 6%. A diminished micturition pressure was also seen after pinacidil (by 18 +/- 8%) but this did not achieve statistical significance. Further, no clear-cut effects on bladder capacity, residual volume, basal bladder pressure, threshold pressure, bladder compliance or on bladder wall tension were seen in this group of rats neither in the presence of pinacidil nor cromakalim. Rats with bladder hypertrophy exhibited a significant bladder instability during cystometrical investigations. The mean amplitude of the spontaneous bladder contraction exceeded 20 cm. H2O prior to micturition. Administration of pinacidil and cromakalin decreased the spontaneous contractions to 26 +/- 12% and 22 +/- 7%, respectively, of that seen in the absence of the drugs. Furthermore, pinacidil decreased micturition pressure by 61 +/- 12%. Also cromakalim decreased micturition pressure (by 27 +/- 13%) but this effect did not achieve statistical significance. After both pinacidil and cromakalim these rats tended to develop residual urine. In accordance with the results in normal rats pinacidil and cromakalim showed no effects on bladder capacity, basal bladder pressure, threshold pressure, bladder compliance or on bladder wall tension in rats with bladder hypertrophy. The findings of an almost complete disappearance of spontaneous bladder contractions in rats with bladder instability and a remaining voiding ability after administration of pinacidil or cromakalim suggest that potassium channel openers may be a therapeutic alternative in the treatment of bladder instability associated with outflow obstruction.

Cystometrical and in vitro evaluation of urinary bladder function in rats with streptozotocin-induced diabetes.

Micturition pattern and cystometric characteristics were determined in control rats, and in rats with streptozotocin-induced diabetes (six weeks duration). The diabetic rats had an increased frequency of micturition, an increased micturition volume, and an increased 24 hr. urinary output. The cystometry showed that the diabetic bladders had an increased compliance and a higher threshold volume for initiating a micturition reflex. No spontaneous rhythmic contractions were seen during the filling phase, and no residual urine could be detected. While micturition pressure increased, the micturition time was virtually unaltered. In vitro a right-ward shift for passive and active length-tension relations was noted. The observed changes in cystometric characteristics and length-tension relations might probably be explained on the basis of adaptive changes to the increased diuresis involving both sensory and motor control of the urinary bladder.

Tetrodotoxin-resistant contractions induced by electrical stimulation of bladder muscle from man, rabbit and rat.

Isolated detrusor preparations from man, rabbit and rat were suspended in an organ bath and isometric tension was recorded. The preparations were stimulated electrically in the presence of Bay K8644 and nifedipine before and after neuronal blockade with tetrodotoxin. Transmural electrical stimulation produced frequency-dependent contractions in all preparations. Bay K8644 significantly increased and nifedipine decreased these contractions. TTX effectively suppressed the response to electrical field stimulation in all species. When Bay K8644 was added to TTX blocked preparations, the responses to electrical stimulation were partly restored in bladder strips from man and rat. No increase in response was seen in the rabbit preparations. However, if the extracellular K+-concentration was increased to 10 mM (which per se did not affect the response) Bay K8644 significantly increased the contractions. All responses elicited by electrical stimulation in the presence of TTX were abolished by nifedipine. It is concluded that if the bladder smooth muscle is exposed to factors that can increase its sensitivity to contractile agents, this may result in uncontrolled (unstable) bladder contractions. Such contractions may use the 'normal' transmitter substances, but may be triggered at a lower stimulus intensity than normal. As a non-specific increase in membrane excitability seems to be associated with an influx of calcium through voltage-sensitive calcium channels, calcium antagonists, together with agents specifically blocking relevant transmitter substances, would offer an effective therapy against the unstable bladder.

Effects of pinacidil on bladder muscle.

Infravesical outflow obstruction and bladder hypertrophy are often associated with bladder hyperactivity causing frequency, urge and urinary incontinence. This hyperactivity may be due to a supersensitivity to depolarising stimuli. Drugs that inhibit smooth muscle activity by opening K+ channels, resulting in hyperpolarisation, would therefore seem to be an attractive therapeutic principle. Pinacidil is an effective vasodilator classified as a K+ channel opener. The drug has been shown to effectively depress spontaneous contractile activity, the contractions induced by low (less than 40 mmol/L) concentrations of K+, carbachol and by electrical stimulation of nerves in isolated normal human bladder tissue and also in normal and hypertrophied rat bladder. The effect was more pronounced in hypertrophied detrusor. Pinacidil in concentrations inhibiting muscle activity also increased the efflux of 86Rb in bladder tissue. In vivo pinacidil suppressed spontaneous contractile activity in rats with infravesical bladder obstruction and detrusor hypertrophy. The findings make K+ channel openers an interesting, potentially useful therapeutic principle in hyperactivity associated with bladder hypertrophy.

Cystometrical evaluation of bladder instability in rats with infravesical outflow obstruction.

Cystometries were performed in normal rats and in rats with bladder hypertrophy due to infravesical outflow obstruction. Investigations were performed in the presence and absence of anesthesia. pentobarbital anesthesia depressed spontaneous contractile activity in the bladder and the micturition reflex, thereby making measurements of other variables, such as bladder capacity and residual volume, impossible. In conscious animals infravesical outflow obstruction led to development of increased bladder capacity, marked residual volume, and unstable detrusor contractions. The model seems to be well suited for further evaluation of the mechanisms involved in the development of detrusor instability and the responses to pharmacological treatment.