Effects of seasonal photoperiod on serum 25-hydroxycholecalciferol and calcium in reindeer, Rangifer tarandus tarandus.

In order to understand the effects of solar irradiance on calcium metabolism we measured serum 25-hydroxycholecalciferol and total calcium levels monthly in 6 female nonpregnant reindeer maintained in the Oulu area (65 degrees N). Mean monthly serum total calcium levels varied slightly and the highest levels were seen in October. Serum 25-hydroxycholecalciferol levels were highest in October but the monthly variation was also slight. The small monthly variation of the analytes' abundance and the fact that they peaked not until 4 months after the longest day, (i.e. the main stimulus for vitamin D synthesis) could have something to do with the supplementation of this vitamin in the diet of the captive reindeer.

Effects on dogs of surface-induced hypothermia and rewarming on the right heart function and pulmonary circulation.

Hypothermia is commonly found in accidents on land and at sea, yet its pulmonary circulatory effects have not been studied before. To study the effects of hypothermia on the right heart function and pulmonary circulation, cardiac catheterization was carried out on nine anaesthetized beagle dogs. The dogs were cooled between ice bags until the temperature in the pulmonary artery was 25 degrees C and then rewarmed using a heating box especially constructed for this purpose. Heart rate decreased significantly (P < 0.01) during cooling. Cardiac output also diminished mainly because of decreased heart rate. Total pulmonary resistance increased in the cold (P < 0.05) and returned to the initial level during rewarming. The peak rate of increase in pressure (dP/dtmax) of the right ventricular pressure curve did not show any significant change. Retardation in relaxation in hypothermia was indicated by an increase (P < 0.01) in the peak negative dP/dt of the right ventricular pressure curve. According to our results, the contraction rate did not change, but the relaxation rate decreased significantly during cooling. No signs of heart failure were observed and all parameters returned to normal during rewarming. In conclusion, right ventricular function was not compromised even during deep hypothermia.

Annual serum PICP and ICTP and antler growth in female reindeer (Rangifer tarandus tarandus).

Annual cycle of type I collagen formation and degradation and antler growth was studied in six adult female reindeer, Rangifer tarandus tarandus. Blood samples were collected twice a week during 1 year. Antler length was measured weekly during the antler growth period. An assay for human PICP, the carboxyterminal propeptide of type I procollagen, was used as an indicator of type I collagen formation and an assay for bovine ICTP, the carboxyterminal telopeptide of type I collagen, as an indicator of type I collagen degradation. PICP was clearly increased during the antler growth period. Also ICTP was slightly elevated during antler growth, but the highest values were found in autumn and winter. Our statistical analysis revealed that changes in lagged values (from 3 to 6 weeks) of PICP could be linked to the subsequent changes in the growth rate of the antler, although the highest values of PICP were found during the final third of antler growth. ICTP had significant predictive power as well, but the connection with the growth rate seemed more immediate than that of PICP. In conclusion, antler collagen synthesis can be predicted by PICP, but also ICTP was related to the antler growth.

Effects of surface-induced hypothermia and rewarming on canine cardiac contraction-relaxation cycle.

The aims of this study were to elucidate the effects of cooling and rewarming on cardiac contraction-relaxation cycle. Cardiac catheterization was carried out on eleven anaesthetized beagle dogs. The dogs were cooled between icebags until the temperature of the blood in the ascending aorta was 25 degrees C and then rewarmed. Heart rate increased transiently at the beginning of cooling down to 33 degrees C (P < 0.05). Cardiac output first tended to increase until a body temperature of 33 degrees C was achieved but then decreased (P < 0.05). The systolic period lengthened significantly (P < 0.001) when the body temperature decreased from 37 degrees C to 25 degrees C. Cardiac relaxation slowed down linearly with temperature during cooling. The peak value of the first order derivative of the ventricular pressure curve (dP/dtmax) increased at the beginning of cooling down to 33 degrees C, indicating enhanced systolic pressure rise in left ventricle but returned to baseline values at lower temperatures. However the ejection fraction, systolic period and the systemic vascular resistance increased at the temperatures below 33 degrees C despite the unaltered peak dP/dt and thus we conclude that the contraction force is augmented in the hypothermia. All the parameters measured recovered to normal during rewarming and no signs of heart failure were noted during the experiments.

Influence of ethanol on circulation in surface-induced hypothermia and subsequent rewarming.

Hypothermia and ethanol are often closely linked and in hypothermic accidents ethanol is often a contributing factor. To study the effects of ethanol on the circulation in hypothermic conditions, cardiac catheterization was carried out on 18 anaesthetized beagle dogs. They were divided into two groups. One gram of ethanol/kg of b.wt. diluted in saline was infused into the vena cava superior within 30 min to seven dogs. The dogs were then cooled between ice bags until the blood temperature in the ascending aorta was 25 degrees C and they were then rewarmed. The control group of 11 dogs was cooled and rewarmed without ethanol infusion. The heart rate first increased when cooling down to 33 degrees C and decreased thereafter in the control group. In the ethanol group heart rate increased during the ethanol infusion and remained high when cooling down to 33 degrees C and decreased thereafter. Heart rate was higher in the ethanol group throughout the experiments, and during rewarming the difference was significant. In the control group cardiac output first increased until a body temperature of 33 degrees C was achieved but then decreased. In the ethanol group cardiac output started to decrease after ethanol infusion. During rewarming there was a significantly higher cardiac output in the ethanol group, probably due to the higher heart rate. In the cardiac cycle the systolic period prolonged significantly (p < 0.001) in both groups when the body temperature decreased from 37 degrees C to 25 degrees C whereas the diastolic period remained quite stable. The contraction phase was also affected by the cooling. The changes in contraction force cannot be seen in dP/dt alone because dP/dt values first increased significantly when cooling from 37 degrees C to 33 degrees C but then decreased. Ejection fraction, systolic period, and the systemic vascular resistance increased despite the reduction of the dP/dt and thus we conclude that the contraction force is augmented in hypothermia. In the ethanol group the myocardium seems to be depressed due to ethanol. In the early phase of cooling heart rate increased but cardiac output decreased in the ethanol group, indicating the decreased ability of the heart to respond to cooling in the presence of ethanol. The time constant of exponential pressure fall (tau) increased linearly with cooling from 37 degrees C to 25 degrees C and recovered with rewarming in both groups. Changes in negative dP/dt coincided with the changes in the time constant of exponential isovolumic pressure fall. Ethanol did not influence relaxation. All the parameters we checked recovered to normal during rewarming.

The acute dose-dependent effects of ethanol on canine myocardial perfusion.

The acute effects of ethanol (1.0 g/kg and 1.5 g/kg, n = 4 and n = 5, yielding blood concentrations of 1.3 +/- 0.2 mg/ml and 2.4 +/- 0.3 mg/ml) on myocardial perfusion were studied in anesthetized, thoracotomized, artificially ventilated dogs by using a radioactive microsphere technique. The control group (n = 5) received saline. The smaller dose of ethanol decreased perfusion in the left ventricular myocardium from 0.737 +/- 0.122 to 0.555 +/- 0.122 ml/g/min (NS), whereas the greater dose nonsignificantly increased it, from 0.744 +/- 0.115 to 0.819 +/- 0.119 ml/g/min (p < 0.01 between the groups). These changes were most evident in subendocardial layers (p < 0.01 both within the groups and between the groups). The greater dose of ethanol increased systemic vascular resistance (p < 0.01 when compared to the control group). The changes in right ventricular myocardium were insignificant. The acute effect of ethanol on coronary blood flow is dose-dependent with small to moderate doses reducing demand for left ventricular flow but with increasing doses evoking not only an increase in demand for flow but also an increase in flow.

Annual variations in serum thyroid-stimulating hormone and thyroid hormones and in their responses to thyrotrophin-releasing hormone in the reindeer.

The reindeer in its natural habitat is subject to great annual variations in ambient temperature, illumination and nutrition. To ascertain the effect of these environmental factors on thyroid function, serum thyroid-stimulating hormone (TSH), thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) concentrations were measured four times a year (2 June, 8 October, 21 November, and 24 February) in 14 animals housed outdoors at latitude 69 degrees 10'N. They all showed statistically significant (P < 0.05) seasonal changes. Serum TSH and T4 were highest in February (623 +/- 30 ng/ml and 287 +/- 19 nmol/l respectively). TSH was lowest in October (318 +/- 47 ng/ml) and T4 in November (199 +/- 19 nmol/l). The T3 concentration was highest in November (3.0 +/- 0.3 nmol/l) and lowest in June (1.8 +/- 0.2 nmol/l). In contrast, rT3 was highest in June (3.6 +/- 1.2 nmol/l) and lowest in November (1.9 +/- 0.6 nmol/l). Thus, there was an inverse relationship between T3 and rT3 (linear regression r = -0.406, P < 0.01). TSH, T4, T3 and rT3 responses to exogenous thyrotrophin-releasing hormone (synthetic TRH; 500 micrograms i.m.) were determined in ten animals. The magnitude of their response to TRH was significantly (P < 0.05) dependent on the time of year. When compared with the control level all the parameters rose significantly (P < 0.05). The greatest rise in serum TSH occurred in October (219 +/- 151%) and the smallest in February (66 +/- 53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Thermal properties of thermodilution catheters.

A suitability of thermodilution catheters to hypothermic conditions was investigated. Thermal properties of two types of thermodilution catheters (Edwards and Spectramed) were checked within a temperature range of 37 degrees C to 22 degrees C. The linear calibration method normally used in normothermia appeared to be inadequate because of the non-linear character of the temperature-resistance curve of the thermistor probe. The best calibration was obtained by using second order formula (ax2 + bx + c) that was fitted to measured temperature-resistance points. An exponential calibration was also tested, but the correlation of the fit was not as good than in the case of the polynome. The absolute variation of resistance of catheters at 37 degrees C was large. If the catheters are calibrated according to mean values, the error in temperature determination was about 1 degree C at normothermia. Erroneously measured temperatures in hypothermia give false cardiac output measurements, which can be dangerous in clinical practice.

The acute dose-related effects of ethanol on right ventricular function in anesthetized dogs.

The acute dose-related effects of small to moderate doses of ethanol on right ventricular functioning were studied on 18 anesthetized, artificially ventilated dogs in 39 sessions. Diluted ethanol (from 25-37.5%) was infused during 40 minutes, yielding total doses of 1.0 g/kg (n = 15), and 1.5 g/kg (n = 12) with corresponding venous blood ethanol peak concentrations of 1.38 +/- 0.25 and 2.41 +/- 0.31 mg/ml, respectively. Heart rate increased up to 16% in groups receiving ethanol. In the control group receiving the equivalent volume of saline (n = 12) heart rate decreased 14%. Pulmonary arterial systolic pressure increased from 24 +/- 3 to 27 +/- 3 mmHg and diastolic pressure from 11 +/- 2 to 14 +/- 4 mmHg (p less than 0.05) when the ethanol dose was 1.0 g/kg. The pulmonary arterial resistance increased from 620 +/- 135 to 805 +/- 185 dyn.s.cm-5 (p less than 0.01). The peak dP/dt decreased maximally by 20% with increasing ethanol doses. Stroke volume decreased maximally by 14% but due to the increase in heart rate, cardiac output even increased. The changes in end-diastolic volume and pressure were not significant. Hence, the ethanol increased heart rate and afterload of the right ventricle but depressed the myocardium.

Seasonal and daily patterns in melatonin secretion in female reindeer and their calves.

Daily patterns of pineal function were studied in different seasons in 10 adult semidomesticated female reindeer and 5 prepubertal calves living in a natural arctic environment at latitude 69 degrees 10'N. Serum samples for melatonin RIA were collected every 4 h for 24 h in October (10 h of light, 14 h of darkness and 8 h of light, 16 h of darkness), December (24 h of darkness), March (13 h of light, 11 h of darkness), and June (24 h of light). A significant daily variation in serum melatonin levels was observed in the adult reindeer, with peak values (20-50 ng/liter) occurring during the night in autumn, winter, and spring, but not summer. The daytime values at 13 h (5-10 ng/liter) were constant throughout the year. Total daily amounts of melatonin, the duration of peak levels, and maximal concentrations were significantly lower in spring and summer than before the rut in autumn. The exposure of adult animals to artificial darkness from bright sunlight on August 1 and September 21 resulted in an immediate increase in serum melatonin concentrations. The 2-week-old calves had detectable serum melatonin levels, but no daily rhythm in the spring, whereas a rhythm was detectable by the first autumn, only to disappear unexpectedly during the first winter and return in the spring. At the age of 16 months, the calves had serum melatonin concentrations similar to those in the adults. Our present results show that the continuous illumination experienced during the summer abolished the normal daily melatonin rhythm. This does not seem to be related to organic changes in the pineal gland, since exposure to darkness during the summer increased melatonin levels. The highest melatonin secretion occurred in the autumn and was evidently associated with the rut. Similarly, the daily melatonin rhythm of an adult type observed in the calves at the age of 16 months may be related to the observation that most calves were in rut. Thus, a high rhythmical melatonin secretion appears to relate to puberty and the initiation of heat in female reindeer.

Cardiac function in hypothermia.

Hypothermia retards cardiac contraction and prolongs the subphases of the cardiac cycle in varying degrees. Six anaesthetized beagle dogs were catheterized and cooled between ice bags until the aortic blood temperature was 25 degrees C and then rewarmed to normothermia. The speed of relaxation decreased to a half from its value in normothermia as indicated by the time constant of exponential isovolumic ventricular pressure fall and by the change in the negative dp/dt. It is suggested that retardation of relaxation is connected with temperature dependent changes in calcium kinetics. Decrease of cardiac output was mediated mainly by decreased stroke volume indicating sympathetic tone in spite of cold narcosis.

Spontaneous oscillation of systemic arterial pressure during cardiopulmonary bypass in the dog.

Cardiopulmonary bypass and an open-heart operation were carried out on four beagle dogs kept under ketamine anesthesia. Oscillation of systemic arterial pressure during this maneuver was observed in three dogs and oscillation of pulmonary arterial pressure in two dogs. Mean amplitude of the oscillation in systemic arterial pressure was 6 to 7 mm Hg and that in pulmonary arterial pressure about 1 mm Hg. The duration of an oscillatory wave was about 20 s. Systemic arterial pressure was 130 to 150 mm Hg. The oscillation disappeared in two dogs when weaning from the bypass. These oscillations resemble those observed in humans during cardiopulmonary bypass and also those observed in experimental animals without bypass conditions.

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)

Mean outflow resistance as a marker of left ventricular afterload.

The changes of mean outflow resistance (MOR) (defined as the ratio between mean aortic ejection pressure and mean ejection rate) and of total peripheral resistance (TPR) together with their relations to some circulatory parameters and to each other were studied under control (NaCl) and six different loading conditions on anesthetized closed chest dogs. Phenylephrine increased both MOR and TPR (ca. 160%, max), pacing increased MOR (p less than 0.01) but not TPR. Isoproterenol and dextran infusion decreased TPR (p less than 0.001) but not MOR. Calcium chloride decreased MOR (p less than 0.05) but increased TPR (NS). The relationship between MOR and TPR was linear in each case (r from 0.63 to 0.91). Both MOR and TPR showed either positive or negative linear correlations with volume and pressure parameters although MOR appeared to be more sensitive to the administered interventions. The present results suggest that, when referring to the pulsatile and discrete nature of the blood-flow-pressure output from the left ventricle, MOR seems to be a more useful measure than TPR in the assessment of the left ventricular afterload.

Spontaneous oscillation of the systemic arterial pressure during cardiopulmonary bypass in man. The effects of some drugs used during the operation.

Despite the fact that the blood flow maintained during cardiopulmonary bypass is rather steady in the extracorporeal pump output, the arterial pressure under high-dose fentanyl anaesthesia quite often shows sinusoidal oscillations. In the present study the duration of an oscillatory cycle was on average 17.6 +/- 3.6 s, its amplitude 7.3 +/- 1.6 mm Hg and mean systemic arterial pressure 75 +/- 12 mm Hg. The oscillation is affected by the drugs used under bypass conditions. In our series of clinical observations the blood pressure oscillation disappeared under the influence of chlorpromazine, phentolamine, droperidol, and enflurane, and it disappeared or at least was distinctly attenuated under fentanyl, thiopental, diazepam, sodium nitroprusside, nitroglycerin, acebutolol, and potassium chloride. Pancuronium, atropine and furosemide appeared to be practically ineffective. In spite of the fact that the drugs used affected several sites of the sympathetic efferent chain, the disappearance and attenuation of the oscillation were associated with a simultaneous decrease of blood pressure. Hence, it is suggested that the occurrence of the oscillations requires some level of peripheral vascular tone.

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.

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.

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.

Spontaneous oscillations of systemic arterial pressure during cardiopulmonary bypass in man.

Extracorporeal blood circulation (ECC) provides a steady flow and minimal pulmonary circulation in the absence of cardiac function. Oscillations of systemic arterial pressure were observed in 70 patients during ECC. At the onset of oscillations the frequency was as a rule 4 cycles per minute but depended on the temperature and showed a positive correlation with it. Correspondingly, the amplitude was about 6 mm Hg and depended on aortic pressure and showed a positive correlation with it. During the cooling phase of ECC the frequency decreased and the amplitude increased. The oscillations were independent of central venous pressure and ventilation. The oscillations disappeared either at the beginning of restitution of cardiac function or with decreasing arterial pressure caused by drug administration or rewarming. Arterial blood pressure oscillations have been described in experimental animals under various conditions but also in conscious man. The mechanisms underlying these oscillations are suggested to be nervous in origin, as is possible also in the present findings.