PubMed HealthSearch

Biomedical subjects

M Vornanen

Publications and source records attributed to M Vornanen.

14 recordsLinked to original sources

Force-frequency relationship, contraction duration and recirculating fraction of calcium in postnatally developing rat heart ventricles: correlation with heart rate.

Heart rates (HR) of awake unrestrained animals, isometric contraction duration and force-frequency relationship of ventricular tissue were determined in adult and postnatally developing rats. Resting HR was lowest in newborns (256 beats min-1), reached maximum at the age of 2.5 weeks (506 beats min-1) and then declined to the level of adult rats (381 beats min-1). Duration of isometric contraction correlated negatively with HR. Time to peak tension (TPT) was 185 ms in newborns but fell rapidly during the first days of post-natal life. Minimum was attained at the age of 2.5 weeks (TPT = 98 ms), followed by a slight prolongation towards adulthood. Recirculating fraction of activator Ca2+ increased parallel with HR, being 6% in newborns, 33% in 11-day-old pre-weanlings, and 87% in adult rats. Similar developmental pattern of the parameters suggests that a post-natal increase in HR and a shortening of contraction duration are closely associated with a shift from extracellular to intracellular source of activator Ca2+. Force-frequency curves were similar at different developmental stages and consisted of three phases; a negative staircase between 0.05 and 1.0 Hz, a positive staircase between 1.0 and 4.0 Hz, and a secondary decline above 4.0 Hz. In adult rats the positive force staircase was weak or absent. Furthermore, our results show that negative staircase is not only a property of adult rat heart but is present, and even more pronounced, in pre-weanling and weanling rat heart. Therefore negative staircase is not solely explained by quantitative changes in the contribution of sarcoplasmic reticulum (SR) to contractile activation, but rather by the mechanisms which regulate loading and/or release of sarcoplasmic reticular Ca2+.

Animals

Maximum heart rate of soricine shrews: correlation with contractile properties and myosin composition.

Maximum heart rates (HR) of three soricine shrews and six other small mammals were measured in response to a single supramaximal dose of isoproterenol (Iso) under urethan anesthesia. The highest HR, 1,043 +/- 66 (SD) beats/min (n = 3), was in least shrew (Sorex minutus, mean body mass 3.02 +/- 0.81 g). Maximum HRs of common shrew (Sorex araneus, 7.16 +/- 1.54 g) and water shrew (Neomys fodiens, 12.80 +/- 1.54 g) were 938 +/- 29 (n = 7) and 887 +/- 21 (n = 6), respectively. In general, maximum HRs of soricine shrews and other small wild mammals followed the common mammalian pattern, fHmax/Iso = 443 x Mb-0.14, determined by body size. The exponent for this equation is smaller than that of resting HR (-0.25) (Stahl, J. Appl. Physiol. 22: 453-460, 1967), predicting crossover at approximately 3 g body mass. However, resting HRs of small mammals were clearly lower than expected on the basis of body mass. Lowering resting HR below the common mammalian level, with concomitant increase in stroke volume, seems to be a prerequisite for small mammals to regulate cardiac output against the ceiling of maximum HR. Electrophoretic analysis showed that the myosin of shrew ventricles is different from those of rodent species. In native conditions, shrew myosin, designated V1', migrated faster than the V3 and V1 forms of rat heart. On SDS gradient gel the single heavy chain of shrew myosin migrated slower than the alpha- or beta-chains of rat ventricle. Differences in the molecular weight of light chains were also noted between small mammals. Despite the notable differences in myosin composition, myosin-ATPase activity of the shrew hearts was similar to that of mouse and rat heart. Because duration of isometric contraction was inversely related to resting and maximum HRs, it was concluded that in the small mammals rate and duration of contraction are determined mainly by the release and uptake rate of myoplasmic Ca2+ and less by myosin-ATPase activity.

Animals

Force measurements from voltage-clamped guinea pig ventricular myocytes.

We describe the first observations of isolated mammalian guinea pig ventricular myocytes that combine measurements of contractile force with the voltage-clamp method. The myocytes were attached by poly-L-lysine to the beveled ends of a pair of thin glass rods having a compliance of 0.76 m/N. The contractile force of a cell caused a 1- to 3-microm displacement of the rods; the motion of which was converted to an output voltage by phototransistors. By the use of the whole cell patch-clamp technique, the cells were depolarized at 1 Hz with 200-ms-long clamp pulses from -45 to +5 mV (35 degrees C, 3.6 mM CaCl2). Isometric force began after a latency of 7 +/- 2 ms, peaked at 93 +/- 21 ms, and relaxed (90%) at 235 +/- 63 ms. The time course of force was always faster than that of isotonic shortening (time to peak 154 +/- 18 ms). With 400-ms-long depolarizations, a tonic component was recorded as either sustained force or sustained shortening that decayed on repolarization. Substitution of Ca by Sr in the bath increased the inward current through Ca channels but slowed down the time course of force development. The results are consistent with the hypothesis that activator calcium derives mainly from internal stores and that Ca release needs Ca entry through channels.

Administration, Topical

Extranodal head and neck non-Hodgkin's lymphomas in children in Finland.

During the 20-year period from 1961 to 1980, 17 cases of extranodal head and neck non-Hodgkin's lymphoma in children under 15 years of age were diagnosed in Finland. Eight cases had tumours in tonsils or nasopharyngeal adenoids and 9 cases lymphomas of other sites of the head and neck. The age-adjusted annual incidence rate for all cases was 0.69 and for tumours of the pharyngeal lymphatic tissue 0.35 per 10(6) children. Seven of the 17 tumours were undifferentiated lymphomas (Burkitt's and non-Burkitt's types) and 5 lymphoblastic lymphomas. The overall 5-year disease-free survival rate was 37%. Five of the 9 patients with tonsillar or adenoid lymphomas were disease-free more than 5 years.

Adenoids

Basic functional properties of the cardiac muscle of the common shrew (Sorex araneus) and some other small mammals.

The resting heartbeat frequency of all the studied wild small mammals (body mass 3-20 g) was lower than that predicted by the allometric equation for a typical mammal. The heart rate of the laboratory mouse was a little higher than the expected value. The ventricular mass of the small wild mammals was higher than predicted for their size, but that of the laboratory mouse was below the expected value. Thus, adequate cardiac output in the wild small mammals is achieved by compensating the low heartbeat frequency with greater stroke volume. The shrew species are notable exceptions, which, despite having a metabolic rate 2-3 times higher than the mammalian average, neither have exceptionally high heart rates nor larger hearts than other wild small mammals. The adaptation of the shrew heart to high metabolic rate may reside in the shape of heart. The ventricular myocardium of shrews is characteristically long and narrow with a tapered apex, whereas other small mammals have rounder hearts. The duration of the ventricular action potential was short and inversely proportional to the resting heart rate of the mammalian species. Caffeine (5 mmol l-1) strongly decreased the isometric contractile force of right ventricular strips in all the studied mammals. These findings suggest that in the small mammals intracellular stores are the main source of activating Ca2+, whereas transsarcolemmal Ca2+ movement may only serve the triggering function.

Action Potentials

Postnatal development of beta-adrenergic response in ventricular muscle of the rat heart.

In adult mammalian, heart responses to beta- and alpha-adrenergic stimulation are different: the beta-type effect exhibits a larger increase of relaxation than of contraction, while the alpha-stimulation has no selective influence on relaxation. The present results show that the effect of isoprenaline (ISO) on the neonatal rat heart during the 1st postnatal week is not a typical beta-effect in that the relaxant influence of beta-stimulation is lacking. During the 2nd and 3rd postnatal weeks the typical beta-response, with improved relaxation, gradually appears. The absence of the typical beta-effect is not caused by the lack of beta-receptors or cAMP-dependent phosphorylation reactions because in other respects, the positive inotropic effect of ISO is well developed at the moment of birth. In addition to these qualitative changes, also prominent quantitative changes occurred in the ISO response. The dose-response curves were shifted to the right with advancing age, suggesting reduced beta-agonist potency of the maturing tissue. The developed tension (Tmax) abruptly increased between the 12th and 17th postnatal days and then steeply declined during the next 2 weeks. Changes in Tmax correlated fairly well with the general ability of the tissue to generate extra force, as expressed by rest-dependent potentiation of twitch. However, during the 2nd postnatal week cardiac tissue seemed to be subsensitive to ISO, since all contractile parameters except T''max were depressed. The results suggest that the postnatal changes in beta-response are primarily determined by alternations in the electromechanical coupling process of the developing tissue, and less by the proper adrenergic mechanisms.

Adrenergic beta-Agonists

Oral cancer in children under 15 years of age. A clinicopathological and virological study.

11 malignant tumours of the oral region in children under 15 years of age were diagnosed in Finland during the 20-year period from 1961 to 1980; the age adjusted annual incidence rate being 0.31 per 1,000,000 children. 5 cases were intraoral cancer and 5 cases malignant tumours of the major salivary glands. The formalin-fixed tumours were studied using the in situ DNA hybridization technique for Adenovirus, group II, Epstein-Barr and human papillomavirus, type 16. For the first time, evidence was provided for the presence of Epstein-Barr virus in a malignant salivary gland tumour, implicating a possible etiological role for this virus in salivary gland neoplasms.

Adolescent

Sarcolemmal ATPase activities of the rat heart ventricle--dependence on age and sodium ion.

Na-K-ATPase activity of the rat heart was similar throughout the postnatal growth when measured from crude unpurified fraction. Instead in the cardiac sarcolemmal fraction, isolated by hypotonic shock LiBr-treatment method, the activity was over two times higher in 10-day old neonates than in adult rats. The conflicting results are partly explained by different effects of the isolation procedure on neonatal and adult tissues. Na concentration for half-maximal activity of the Na-K-ATPase was similar in neonates (7.0 mM) and adults (6.4 mM). Ca-ATPase activity was not affected by Na concentration (2-100 mM) in the two age-groups studied.

Aging

Effects of procaine and caffeine on the contractility of enzymatically isolated myocytes and intact cardiac tissue.

1. Procaine and caffeine exerted opposite effects on the contractility of rat cardiac tissue. 2. Procaine enhanced and caffeine depressed isometric contractile force of right ventricular strips. 3. In enzymatically isolated cells, caffeine increased the frequency and decreased the amplitude of spontaneous contractions, while procaine retarded the beating rate but concomitantly raised the shortening amplitude of the myocyte. 4. Both drugs depressed the propagation velocity of the contractile waves. 5. The results are suggested to be due to the opposite effects of the two drugs on the Ca-release process of the sarcoplasmic reticulum.

Animals

Activation of contractility and occurrence of aftercontractions in Ca2+ and Sr2+-solutions during the postnatal development of the rat heart.

Activation of isometric contractile force and induction of aftercontractions by different extracellular Ca- and Sr-concentrations during the early postnatal development of the rat heart were studied. In the neonatal (1-15 days) rat heart activation of contractility by [Ca]0 and [Sr]0 were similar when a dose-response curve for Ca was determined before Sr, but if the experiment was performed in the reverse order of the dose-response curve for Sr was shifted to the left. In either case the maximal developed tension was about the same. In the adult (3-5 months) rat heart [Ca]0 higher than 4 mM was inhibitory, whereas contractile force increased up to 16 mM [Sr]0 without any signs of force depression. The dose-response curve for Sr was shifted to the right compared to that of Ca and the maximal developed tension was clearly higher in Sr-solution than in Ca-solution. Aftercontractions appeared for the first time on the 13th and 24th postnatal days for 16 mM [Ca]0 and [Sr]0, respectively. In the adult rat ventricle lower Ca concentrations were needed to induce aftercontractions compared to Sr. Based upon these observations it is suggested that the appearance of aftercontractions during the third postnatal week of rat heart development is due to the maturation of intracellular Ca stores which become available for contractile activation by the development of the T-system. The absence of a negative inotropic effect in elevated Sr concentrations may be due to the slowing down of the transport processes of the sarcoplasmic reticulum (SR) by Sr and to the greater ability of the SR to store Sr over Ca.

Age Factors

Effect of strontium on the contractile properties of postnatally developing rat heart ventricles.

The effects of substitution of calcium (Ca) by an equimolar concentration of strontium (Sr) on isometric contractions of isolated ventricular muscle from postnatally developing rat heart were studied. The duration of contraction and the time-to-peak tension were increased in all age groups although much less in the adult rats than in the neonates. The contractile force was increased in the muscles of rats between 1 and 14 days of age but was depressed in the older animals. The prominent rest-twitch potentiation of neonatal rat heart in Ca-Tyrode was totally eliminated by Sr, whereas a clear rest-twitch potentiation was induced by this cation in the adult rat heart, in which tissue the potentiation is normally absent in Ca-Tyrode. The maximal twitch potentiation by rest in Ca-Tyrode and the positive inotropic effect of Sr substitution grew from birth up to day 9 and from then gradually declined towards the level of adult rat heart by the end of the 3rd postnatal week. The phase of increasing rest-twitch potentiation coincides fairly well with the known development of sarcoplasmic reticulum and the phase of decline with the appearance of the T system of the sarcolemma. It is suggested that the qualitative changes in the contractile properties of developing rat heart during the 3rd postnatal week are due to the more efficient utilization of intracellular calcium stores, owing to the development of the T system.

Animals

Postnatal changes in the inotropic effect of ouabain on the rat heart ventricle.

The concentration-dependent effects of ouabain on the contractility of postnatally developing rat heart ventricles were studied. Ouabain caused a positive inotropic effect in right ventricular strips of neonatal rats up to the age of about 30 days but a negative inotropic effect in the adult cardiac tissue. When extracellular Ca concentration was lowered from 2.5 to 1.0 mmol/l and the rate of stimulation was simultaneously elevated from 0.2 to 1.0 Hz a clear positive inotropic effect was also generated in the adult rat heart. The positive inotropic effect of ouabain showed a biphasic developmental pattern: the contractile force first grew from birth to about 15 days of age but steeply declined near to the adult level during the 3rd postnatal week. The force response to ouabain occurred within two distinct dose-ranges. In the newborn only the high-dose (above 3 X 10(-6) mol/l) effect was seen but in rats older than 5 days a mixed low-dose (below 3 X 10(-6) mole/l)/high-dose effect was apparent. In both ranges the positive inotropic effect of ouabain seemed to be dependent on caffeine sensitive Ca store, perhaps the sarcoplasmic reticulum. It is suggested that during the 3rd postnatal week a transition from extracellular to intracellular Ca stores occurs in the rat heart, which is reflected as a changing inotropic effect of ouabain on the developing cardiac tissue.

Animals