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R Kettunen

Publications and source records attributed to R Kettunen.

At least 37 records · Page 2Linked to original sources

ATP and light regulate D1 protein modification and degradation. Role of D1* in photoinhibition.

We have recently shown that during in vivo photoinhibition the D1 protein is degraded via a modified form, designated D1*. Depending on light conditions, the amount of D1* varies in leaves between 0 and 50% of total D1 content. By isolating thylakoids from leaves acclimated to different light levels, and performing photoinhibition experiments on these thylakoids, the following results on D1 protein degradation were obtained: (i) the protease involved in D1 degradation requires activation by light; (ii) neither acceptor nor donor side photoinhibition of PSII induces formation of D1* in vitro; (iii) in isolated thylakoids, the transformation of D1 to D1* can be induced in low light in the presence of ATP, which suggests that D1* is a phosphorylated form of the D1 protein; (iv) D1*, induced either in vivo or in vitro, is much less susceptible to degradation during illumination of isolated thylakoids than the original D1 protein. We suggest that the modification to D1* is a means to prevent disassembly of photodamaged photosystem II complex in appressed membranes.

Adenosine Triphosphate↗

Slow degradation of the d1 protein is related to the susceptibility of low-light-grown pumpkin plants to photoinhibition.

Photoinhibition of photosystem II (PSII) electron transport and subsequent degradation of the D1 protein were studied in pumpkin (Cucurbita pepo L.) leaves developed under high (1000 mumol m(-2) s(-1)) and low (80 mumol m(-2) s(-1)) photon flux densities. The low-light leaves were more susceptible to high light. This difference was greatly diminished when illumination was performed in the presence of chloramphenicol, indicating that a poor capacity to repair photodamaged PSII centers is decisive in the susceptibility of low-light leaves to photoinhibition. In fact, the first phases of the repair cycle, degradation and removal of photodamaged D1 protein from the reaction center complex, occurred slowly in low-light leaves, whereas in high-light leaves the degradation of the D1 protein more readily followed photoinhibition of PSII electron transport. A modified form of the D1 protein, with slightly slower electrophoretic mobility than the original D1, accumulated in the appressed thylakoid membranes of low-light leaves during illumination and was subsequently degraded only slowly.

Journal Article↗

D1 protein degradation during photoinhibition of intact leaves. A modification of the D1 protein precedes degradation.

Illumination of intact pumpkin leaves with high light led to severe photoinhibition of photosystem II with no net degradation of the D1 protein. Instead, however, a modified form of D1 protein with slightly slower electrophoretic mobility was induced with corresponding loss in the original form of the D1 protein. When the leaves were illuminated in the presence of chloramphenicol the modified form was degraded, which led to a decrease in the total amount of the D1 protein. Subfractionation of the thylakoid membranes further supported the conclusion that the novel form of the D1 protein was not a precursor but a high-light modified form that was subsequently degraded.

Blotting, Western↗

Usefulness of technetium-99m-MIBI and thallium-201 in tomographic imaging combined with high-dose dipyridamole and handgrip exercise for detecting coronary artery disease.

Forty-two patients with known stable coronary artery disease, referred for coronary angiography, were examined with technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile (MIBI) tomography combined with a high-dose dipyridamole infusion (0.7 mg/kg) and handgrip stress. MIBI tomography was unable to show coronary artery disease only in 2 patients, thus yielding a sensitivity figure of 95%. MIBI tomography correctly identified 27 (82%) of 33 stenotic lesions (greater than or equal to 50% diameter stenosis) of the left anterior descending artery, 17 (61%) of 28 of those of the left circumflex artery, and 28 (90%) of 31 of those of the right coronary artery. The overall vessel sensitivity was 78%. The computed lumen diameter stenoses were more advanced in cases detected than in those not detected with MIBI tomography: 87 +/- 14 vs 76 +/- 14% (p less than 0.01). The 50 to 69% stenoses did not show any tendency to produce less positive findings than those with greater than or equal to 70% stenoses. In the subgroup of 21 patients who also presented for thallium scintigraphy, the overall diseased vessel identification rate was 76% for thallium tomography and 83% for MIBI tomography (p = not significant). Minor noncardiac side effects related to the dipyridamole-handgrip test occurred only in 5% of 63 study sessions. A high-dose dipyridamole combined with isometric exercise is a safe stress method, and when used during scintigraphy, MIBI tomography is at least as efficient a tool as thallium tomography in detecting diseased vessel territories in patients in coronary artery disease.

Aged↗

Effects of training and anabolic steroids on collagen synthesis in dog heart.

The effects of endurance training and anabolic steroid (Methandienone 1.5 mg.kg-1 p. o. daily) and their combination on regional collagen biosynthesis and concentration in the hearts of male beagle dogs were studied by measuring prolyl 4-hydroxylase (PH) activity and hydroxyproline (HYP) concentration. The PH (P less than 0.05) and HYP (P less than 0.05) were both greater in the subendocardinal layer than in the subepicardium (EPI) of the left ventricular wall in controls, whereas opposite gradients (P less than 0.05) were observed in the right ventricle. Endurance exercise caused an increase of PH activity in EPI of the left ventricular wall (P less than 0.01). The HYP concentration increased in both layers of the right ventricle in the exercise plus steroid group (P less than 0.05). The results suggest that transmural differences exist in the rate of collagen synthesis and concentration in canine cardiac ventricles and that endurance exercise may accelerate collagen synthesis in EPI of the left ventricle and the combination of exercise and anabolic steroid causes an increase in collagen concentration in the right ventricular wall.

Alkaline Phosphatase↗

Left ventricular function in dogs 1 year after coarctectomy.

Juxtaductal aortic coarctation was surgically created in beagle puppies at the age of 2 months and resected at the age of 10 months, after the development of good collateral circulation. Control dogs undergoing sham operations on each occasion were studied in the same environment. Cardiac catheterization was performed 1 year after the coarctectomy to evaluate the recovery of the heart. Cardiac output, heart rate, end-diastolic pressure, and Vmax were similar in both groups of seven dogs, but the systolic pressure gradient (SPG) over the operated area during isoproterenol infusion was significantly higher in the coarctectomized group, with a mean of 8.9 +/- 6.3 (SD) vs. 0.1 +/- 0.3 mmHg (p less than 0.05). The preejection period [PEP, 58 +/- 8 vs. 47 +/- 5 ms (p less than 0.01)], electromechanical delay [EMD, 18 +/- 3 vs. 13 +/- 3 ms (p less than 0.05)], and isometric contraction time [ICT, 39 +/- 7 vs. 32 +/- 4 ms (p less than 0.05)], were all significantly longer in the coarctation group after isoproterenol infusion. The results demonstrate that, even though cardiac output increased adequately during loading and mechanical pumping efficiency was preserved, excitation-contraction coupling was still prolonged. Thus, an anatomical successful coarctectomy, even at the age of 10 months, does not fully restore left ventricular function in dogs after chronic experimental coarctation.

Animals↗

Small light-harvesting antenna does not protect from photoinhibition.

High-light-induced decrease in photosystem II (PSII) electron transfer activity was studied in high- and low-light-grown pumpkin (Cucurbita pepo L.) plants in vivo and in vitro. The PSII light-harvesting antenna of the low-light leaves was estimated to be twice as big as that of the high-light leaves. The low-light leaves were more susceptible to photoinhibition in vivo. However, thylakoids isolated from these two plant materials were equally sensitive to photoinhibition when illuminated in the absence of external electron acceptors. Only the intensity of the photoinhibitory light and the chlorophyll concentration of the sample, not the size of the light-harvesting antenna, determined the rate of PSII photoinhibition in vitro. Because excitation of the reaction center and not only the antenna chlorophylls is a prerequisite for photoinhibition of PSII activity, independence of photoinhibition on antenna size provides support for the hypothesis (Schatz EH, Brock H, Holzwarth AR [1988] Biophys J 54: 397-405) that the excitations of the antenna chlorophylls are in equilibrium with the excitations of the reaction centers. Better tolerance of the high-light leaves in vivo was due to a more active repair process and more powerful protective mechanisms, including photosynthesis. Apparently, some protective mechanism of the high-light-grown plants is at least partially active at low temperature. The protective mechanisms do not appear to function in vitro.

Journal Article↗

Impaired venous return causes circulatory failure in experimental pancreatitic shock in dogs.

The haemodynamic effects in the early phase of canine acute experimental pancreatitis (AP) were studied using a cardiac catheterization technique. AP was induced in anaesthetized dogs with an infusion of trypsin-sodium-taurocholate into the pancreatic duct. The initial haemodynamic measurements were performed after the preparation of the animal and 5 min after the induction of AP. Thereafter, pressure and volume parameters were measured at 10 min intervals. AP induced significant increases in heart rate, dP/dtmax and mean arterial pressure, but a decrease in Vmax 5 min after the induction of AP. After the initial phase, the heart rate remained significantly increased, while constant and significant decreases of stroke volume, cardiac output, end-diastolic volume and end-diastolic pressure developed. The parameters of the contractility of the left ventricle were not affected to the same extent. It is suggested that the circulatory failure observed in AP, characterised by a prompt reduction of cardiac output, was primarily due to a heavy reduction in preload. This supports the theory that cardiac output is primarily affected by impaired venous return with consequently decreased preload rather than by a loss of ventricular contractility. Hence, the existence of a myocardial depressant factor in the early phase of experimental AP does not gain support from the present results.

Acute Disease↗

Anabolic steroids alter the haemodynamic effects of endurance training and deconditioning in rats.

The haemodynamic effects of endurance training with or without anabolic steroid treatment (nandrolone decanoate, 5.0 mg kg-1 week-1) were studied before and after a six-week sedentary period in anaesthetized, open-chest rats during isoproterenol and CaCl2 loads. In comparison to the control group (CG I, n = 13) endurance training (TG I, n = 10) increased the resting stroke index significantly, end-diastolic pressure and during CaCl2 infusion the end-diastolic and end-systolic volumes. Peripheral resistance decreased in TG I during both inotropic loads but increased in CG I (P less than 0.01 between the groups). After combined endurance training and anabolic steroid treatment (TSG I, n = 16) the haemodynamic state was similar to that in CG I except peripheral resistance which was even higher than in CG I. The heart weight to body weight ratio was significantly greater both in TG I and TSG I than in CG I. After a six-week deconditioning period the haemodynamic values were essentially similar in endurance trained (TG II, n = 10) and in control rats (CG II, n = 12). After the sedentary period, in the simultaneously trained and anabolic steroid-treated group (TSG II, n = 13) stroke index and end-diastolic volume decreased more during isoproterenol load when compared with TG II or CG II (P less than 0.05 between the groups). Peripheral resistance was higher in the TSG II than in the two other groups. In conclusion, the enhanced pumping performance of the heart by increased left ventricular diastolic filling after endurance training is attenuated by simultaneous anabolic steroid treatment which further increases the peripheral resistance. Detraining reversed the main training effects in six weeks and simultaneous anabolic steroid treatment led to a decreased left ventricular filling and to elevated peripheral resistance after the sedentary period.

Anabolic Agents↗

The cardiovascular effects of deconditioning after endurance training in rats.

The haemodynamic effects of endurance training and physical deconditioning were studied in anaesthetized rats using aortic and left ventricular pressure recordings and volume measurements by thermodilution method during isoproterenol and CaCl2 loads. The resting stroke volume was significantly larger in the training group (TG I, n = 10) than in the control group (CG I, n = 13). During the CaCl2 infusion stroke index, end-diastolic and end-systolic volumes increased in the TG I, but decreased in the CG I. Both isoproterenol and CaCl2 decreased systemic vascular resistance in the TG I, but increased it in the CG I. After a six-week deconditioning following training period (TG II, n = 10) stroke index, end-diastolic and end-systolic volumes decreased during CaCl2 and isoproterenol infusions similarly to the control deconditioning group (CG II, n = 12). These responses differed significantly from those observed in the TG I. Peripheral resistance increased in both the CG II and the TG II. Cardiac hypertrophy observed during training was partly reversed after the deconditioning period. In conclusion, endurance training improves the pumping performance of the rat heart by enhancing the diastolic filling of the left ventricle and decreasing peripheral resistance during inotropic load. Left ventricular contractility is not affected. A six-week deconditioning period after endurance training returns the haemodynamic changes to sedentary levels.

Animals↗

Anabolic steroids alter the haemodynamic effects of endurance training on the canine left ventricle.

The effects of six week, high-dose anabolic steroid treatment (methandienone, 1.5 mg/kg/day) on the changes in left ventricular function induced in dogs by endurance training were studied by a catheterization technique under anaesthesia. Pacing, isoproterenol and dextran infusions were used as loading tests (respectively). Dogs were randomized into an exercise group (EG, n = 7) and an exercise-steroid group (ESG, n = 7), the latter receiving anabolic steroids as well as participating in the training program. In a standardized submaximal exercise test, the heart rate of unanesthetized dogs was lower both in the EG (p less than 0.001) and in the ESG (p less than 0.01) after the training period than before it. In the EG the resting systemic vascular resistance (SVR) before haemodynamic interventions was lower (p less than 0.05) and left ventricular stroke work (SW) was higher (p less than 0.05) after the training period than before. In the ESG, left ventricular ejection fraction (EF) decreased with training and anabolic steroid treatment (p less than 0.05). After the training period isoproterenol increased the maximum velocity of the cardiac contractile element significantly more (p less than 0.05) in the EG than in the ESG. Also SW increased in the EG (29%, p less than 0.001), but not in the ESG (-11%, NS). Endurance training increased the left ventricular end-diastolic and stroke volumes during isoproterenol infusion, but this training effect was attenuated by simultaneous anabolic steroid treatment (p less than 0.05 between the groups in both cases). During the isoproterenol test SVR decreased less in ESG than in EG (p less than 0.05 between).(ABSTRACT TRUNCATED AT 250 WORDS)

Anabolic Agents↗

The effects of anabolic steroids and endurance training on systolic time intervals in the dog.

The effects of administration of anabolic steroids (SG, n = 6), endurance training (EG, n = 7) and a combination of steroid administration (Methandienone R) and training (ESG, n = 7) on systolic time intervals (STI) in the dog heart were compared with control dogs (CG, n = 7) by a catheterization technique. Isoproterenol infusion was used as a positive inotropic load. Physical performance was checked with submaximal exercise test, a 30 beats min-1 decrease in heart rate response was considered a sufficient training effect. During isoproterenol infusion, exercise was found to enhance the pump performance of left ventricle and increased stroke volume was related to shortened pre-injection period (PEP) (P less than 0.05), whereas steroid administration failed to induce any significant differences in PEP or PEP/LVET (LVET = left ventricular ejection time) when compared with CG. However, when steroid administration was combined with endurance training, both PEP and PEP/LVET were lengthened significantly in comparison with EG (P less than 0.05 and P less than 0.01, respectively). In conclusion, it seems that the anabolic steroids affected the STIs only, when their administration was combined with endurance training.

Anabolic Agents↗

Hemodynamic effects of endurance training on canine left ventricle.

To investigate the effects of endurance training on myocardial performance seven beagle dogs (exercise group, EG) were trained by treadmill running for 6-7 wk. Before and after experimental period the EG and control group (CG, n = 7) underwent a standard submaximal exercise test (SMT), and hemodynamic status was checked during anesthesia by catheterization technique exposing the animals to different loadings: pacing, volume loading, and isoproterenol infusion. The increase of heart rate during SMT was about 30 beats/min less in the EG than in the CG. A highly linear relationship between stroke work and end-diastolic volume was observed within the groups (for EG r = 0.953, for CG r = 0.846), but the slope of the regression line obtained for EG appeared to be significantly (P less than 0.001) greater. In EG isoproterenol induced increases in end-diastolic (27%), end-systolic (37%), and stroke volumes (19%), but, on the contrary, decreases of these volumes in CG (19, 15, and 22%, respectively); ejection fraction remained unchanged for both EG and CG. Ventricular stroke work was significantly greater in EG. Systemic vascular resistance decreased in EG in every loading test. The results indicate an improved pump performance, which is related not only to the heterometric autoregulatory adjustments, but also to extracardial adaptations.

Animals↗

Time constant of isovolumic pressure fall in the intact canine left ventricle.

The two standard methods of computation of the time constant of the isovolumic single exponential decay of the left ventricular pressure were compared in anaesthetised, artificially ventilated, closed chest dogs in 87 experiments. In 23 additional experiments, carried out under basal steady state conditions, the time constant attained a mean (SD) value of 32(5) ms when computed according to the method with zero pressure asymptote assumption (Tz) and 39(7) ms when estimated according to a fit with variable pressure asymptote (Tv). Phenylephrine infusion significantly prolonged Tz from 31(6) to 46(12) and Tv from 39(7) to 92(52) ms. The increase in Tv was significantly greater than that in Tz. Propranolol increased Tv by 50% but Tz remained unaltered. Isoproterenol significantly decreased Tz from 33(2) to 18(3) and Tv from 38(3) to 29(3) ms. The decrease in Tz was significantly greater than that in Tv. Calcium chloride and atrial pacing decreased time constants, but volume loading by dextran infusion did not affect them. With regard to the whole material, the linear regression analysis yielded 0.776 as the coefficient of correlation between Tz and Tv. The two methods of time constant calculation appeared to diverge significantly always when changes in afterload or sympathetic activity were involved. These results indicate the dependence of relaxation on afterload but the independence on preload or ejection timing. In the light of these results the zero pressure asymptote method is recommended for the time constant computation as the practical choice when relaxation of the intact left ventricle is assessed.

Animals↗

The automatic computation of pressure-derived maximal shortening velocity (Vmax) of the unloaded contractile element in the intact canine heart left ventricle.

Estimation of the maximum velocity (Vmax) of the contractile element of the intact left ventricular wall muscle demands extrapolation of the force-velocity curve to zero load. The present paper describes our on-line computation system for measuring and analysing pressure derived Vmax using both linear (Vmax-lin) and exponential (Vmax-exp) extrapolation methods. The developed pressure during isovolumetric phase of systole was used as an equivalent of the force. Testing on anaesthetized artificially ventilated dogs showed the exponential function to fit pressure-velocity data better than the straight line did. The Vmax-exp attained 15-35% greater values than Vmax-lin, but both responded almost equally when considered on the basis of linear regression analysis (r = 0.991, n = 725). Changes of contractility caused by i.v. infusion of isoproterenol, calcium chloride or propranolol were practically similar when assessed by either method of Vmax computation, or by dP/dtmax. Volume loading by dextran infusion increased not only dP/dtmax, by 33 +/- 13%, but also Vmax, up to 24 +/-. When arterial pressure was raised by phenylephrine infusion, or heart rate by atrial pacing, dP/dtmax increased significantly while Vmax remained unaltered. Hence, the linear and exponential dP/dtmax increased significantly while Vmax remained unaltered. Hence, the linear and exponential extrapolation procedures provided comparable values for Vmax, but the linear one due to its simplicity is more suited for on-line computation. The Vmax thus obtained is, however, not independent of the changes in preload.

Animals↗

The thermodilution technique in on-line computation of the left ventricular volumes on anaesthetized dogs.

The thermal dilution technique and its suitability for automatic computation of left ventricular volumes were evaluated on 28 anaesthetized dogs. The end-diastolic volume (EDV) was computed from ventricular washout curves in two ways, first utilizing the ratio between the indicator amount and its peak concentration (first ejection method); and secondly the ratio between stroke volume and ejection fraction with the latter obtained by subtracting the residual fraction from 1.0. The residual fraction was determined as the mean of ratios between successive steps of four ventricular ejections on the downslope of the curve (downslope method). The linear correlation coefficient between the EDV determinations (n = 366) was 0.926, and slope y = 1.14 X + 0.5 ml with 4.6 ml as standard error of estimate. The first ejection method gave on average 15% higher EDV values than the downslope method. When heart rate was increased by pacing from 88 to 240/min, both methods showed a reduction of the EDV, but the downslope method to a greater degree. When afterload was increased but heart rate decreased by phenylephrine, the first ejection method but not the downslope method indicated an increase in EDV. Otherwise, when pronounced tachy- or bradycardia were avoided, ventricular volumes yielded by the two methods were comparable. Indicator injection did not substantially affect ventricular pressure dynamics. The first ejection method seems to be a simple means for repeated measurements of EDV even in the case of diseased hearts.

Animals↗

Electromechanical delay in the intact dog heart.

A computer method was developed for the determination of electromechanical delay defined as the time between the onset of Q-wave and the onset of the left ventricular systolic pressure rise. It was validated for heart catheterization studies on 56 intact anaesthetized beagle dogs in 86 sessions. The mean basal value of the electromechanical delay was 22 +/- 4 msec. Heart rate, contractility, preload and afterload were changed by atrial pacing and by infusions of calcium chloride, isoproterenol, propranolol, dextran and phenylephrine. Increase of heart rate by pacing from the spontaneous rate of 90 per min to 240 per min prolonged the electromechanical delay from 21 +/- 5 to 33 +/- 14 msec (P less than 0.001). Otherwise the duration of electromechanical delay changed independently of the heart rate. If it changed, the direction of the change followed that of the pre-ejection period. Its proportion of the pre-ejection period varied from 26 to 52%. The electromechanical delay shortened when a positive inotropic effect was noticed or the presystolic fibre length increased.

Animals↗

Haemodynamic effects of precordial or carotid ultrasound application on the dog.

Ultrasound (1.09 MHz, 1 to 2 W/cm2) was applied on the thoracic wall or on the neck of the anaesthetized, artificially ventilated dog. The heart rate, stroke volume and cardiac output remained almost unchanged during both applications. The aortic and pulmonary arterial pressures increased by 7 to 9 mmHg. Pulmonary arterial wedge pressure increased. The right atrial mean and aortic and pulmonary arterial pulse pressures did not change. The observed changes except the rise of wedge pressure returned to the control values within 5 min after the application. The present findings suggest an increase in systemic vascular and pulmonary arterial resistances in connection with both methods of ultrasound application. The precordial application was associated with pooling of blood in the pulmonary circuit. Since the ultrasound non-selectively affects several receptors and structures the final role of the sympathetic nervous system can be evaluated after experiments with isolated targets and selected denervations.

Animals↗