In vivo evaluation of the improved MCMS-0102 pacemaker with a rapid pacing mode for induction of experimental heart failure in animals

The MCMS-0102 cardiac pacemaker for rapid ventricular pacing to induce heart failure in animals has been improved in terms of miniaturization and performance. To determine the performance of the new MCMS-0102, six devices were implanted in beagle dogs, and two of these devices were reimplanted for continued pacing in a total of eight beagle dogs. The hearts were paced at 260 beats per minute for 4 weeks (P group: n = 8). The hemodynamic status of the P group was examined and compared with nonpaced dogs (NP group: n = 8). The neurohumoral status of the P group was evaluated before and after rapid pacing. Stable operation of the six devices during rapid pacing was confirmed using the telemetry system. Postmortem examinations revealed features similar to clinical heart failure characterized by massive ascites, pleural effusion, cardiomegaly, and liver congestion in all the paced dogs. Cardiac output was 1.1 ± 0.2 l/min in the NP group and 0.5 ± 0.1 l/min in the P group (P < 0.0001). The left atrial pressure and the central venous pressure of the P group and the NP group were 23 ± 6 versus 6 ± 2 mmHg (P < 0.0001) and 10 ± 3 versus 4 ± 3 mmHg (P < 0.001), respectively. In the paced dogs, plasma renin activity increased from 0.5 ± 0.4 to 8.5 ± 7.4 ng/ml/h (P < 0.05) and atrial natriuretic peptide levels increased from 69 ± 41 to 229 ± 72 pg/ml (P < 0.001). The improved MCMS-0102 was successfully implanted in beagle dogs and it succeeded in inducing the congestive heart failure model.     

Sympathetic stimulation induced by hand cooling alters cold-induced vasodilatation in humans

Hand cooling is a cold pressor test, which induces general sympathetic stimulation. This cooling procedure is often performed to investigate cold induced vasodilatation (CIVD) in one finger. To investigate the effects of this sympathetic stimulation on local CIVD, 12 subjects immersed either the right index finger (T1), right hand (T2) or left hand and right index finger (T3) for 30 min in water at 5°C followed by 15-min recovery. Skin temperature and skin blood flow (Q˙ _sk) measured by laser Doppler flowmetry on the right index finger, as well as heart rate (f _c) and mean arterial blood pressure (), were continuously monitored during the three tests. Cutaneous vascular conductance was calculated as Q˙ _sk/. Concentrations of plasma noradrenaline (NA) and adrenaline (AD) were measured at different times during the tests. The results showed no cardiovascular change in T1, whereas f _c and increased significantly at the beginning of both T2 and T3. Similarly, sympathetic stimulation was reflected in the NA concentrations, which increased significantly (P < 0.01) during T2 and T3 after 5 min of immersion, and remained elevated until the recovery period. The AD concentration did not change during the three tests. During T2, the CIVD appeared later and slower in comparison with T1 [CIVD onset: 12.81 (SEM 2.30) min in T2 and 5.62 (SEM 0.33) min in T1] . During T3, the CIVD onset was not delayed compared to T1 [6.38 (SEM 0.67) min], but the rewarming was lower [+5.40 (SEM 0.86)°C in T3 and +9.10 (SEM 1.31)°C in T1]. These results showed that CIVD could be altered by sympathetic stimulation but it also appeared that the onset of CIVD could be influenced by local cooling, independently of the general sympathetic stimulation. Accepted: 23 September 1999     

Effect of xylazine–ketamine–diazepam anesthesia on certain clinical and arterial blood gas parameters in sheep and goats

This study was conducted to evaluate the effect of xylazine–ketamine–diazepam anesthesia on heart rate, respiration rate, rectal temperature, rumen motility, peripheral blood pH, PaO2, and PaCO2 in adult female nonpregnant Awassi sheep and adult female nonpregnant Damascus goats. Anesthesia was induced using 0.1 mg/kg, 5 mg/kg, and 0.25 mg/kg xylazine, ketamine, and diazepam respectively as a single intravenous injection. The heart rate, respiration rate, rectal temperature, rumen motility, peripheral arterial blood pH, PaO2, and PaCO2 were evaluated 15 min before and at 15, 30, and 60 min during anesthesia. In sheep, the heart rate, rumen motility, and PaO2 were decreased significantly (P < 0.05) at 15, 30, and 60 min following anesthesia. The respiration rate and rectal temperature and blood pH were decreased significantly (P < 0.05) at 30 and 60 min. The peripheral PaCO2 was increased significantly (P < 0.05) at 15 and 30 min. In goats, the heart rate and rumen motility were decreased significantly (P < 0.05) at 15, 30, and 60 min while the respiration rate was decreased only significantly (P < 0.05) at 60 min. Rectal temperature was decreased significantly (P < 0.05) at 30 and 60 min. The blood pH was decreased significantly (P < 0.05) at 15 and 30 min. PaO2 was only significantly (P < 0.05) decreased at 15 min while PaCO2 was increased significantly (P < 0.05) at 15 and 30 min.     

A refined radio-telemetry technique to monitor right ventricle or pulmonary artery pressures in rats: a useful tool in pulmonary hypertension research

Implantable radio-telemetry methodology, allowing for continuous recording of pulmonary haemodynamics, has previously been used to assess effects of therapy on development and treatment of pulmonary hypertension. In the original procedure, rats were subjected to invasive thoracic surgery, which imposes significant stress that may disturb critical aspects of the cardiovascular system and delay recovery. In the present study, we describe and compare the original trans-thoracic approach with a new, simpler trans-diaphragm approach for catheter placement, which avoids the need for surgical invasion of the thorax. Satisfactory overall success rates up to 75% were achieved in both approaches, and right ventricular pressures and heart and respiratory rates normalised within 2 weeks. However, recovery was significantly faster in trans-diaphragm than in trans-thoracic operated animals (6.4 ± 0.5 vs 9.5 ± 1.1 days, respectively; p < 0.05). Stable right ventricular pressures were recorded for more than 4 months, and pressure changes, induced by monocrotaline or pulmonary embolisms, were readily detected. The data demonstrate that right ventricular telemetry is a practicable procedure and a useful tool in pulmonary hypertension research in rats, especially when used in combination with echocardiography. We conclude that the described trans-diaphragm approach should be considered as the method of choice, for it is less invasive and simpler to perform. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.     

A single open sea air dive increases pulmonary artery pressure and reduces right ventricular function in professional divers

After decompression from dives, bubbles are frequently observed in the right ventricular outflow tract and may lead to vascular damage, pulmonary arterial hypertension and right ventricular overload. No data exist on the effect of open sea diving on the pulmonary artery pressure (PAP). Eight professional divers performed an open sea air dive to 30 msw. Before and postdive a Doppler echocardiographic study was undertaken. Systolic pulmonary artery pressure (SPAP) was estimated from measurement of peak flow velocity of the tricuspid regurgitant jet; the ratio between pulmonary artery acceleration times (AccT) and right ventricular ejection time (RVET) was used as an estimate of the mean PAP. No evidence of either patent foramen ovale or intra-pulmonary shunt was found in any subject postdive after performing a Valsalva maneuver. SPAP increased from 25 ± 3 to 33 ± 2 mmHg and AccT/RVET ratio decreased from 0.44 ± 0.04 to 0.3 ± 0.02 20 min after the dive, respectively. Pulmonary vascular resistance increased from 1.2 ± 0.1 to 1.4 ± 0.1 Woods Units. Postdive right ventricle end-diastolic and end-systolic volumes were increased for about 19% (P = 0.001) and 33% (P = 0.001) and right ejection fraction decreased about for 6% (P = 0.001). Cardiac output decreased from 4.8 ± 0.9 (l min⁻¹) to 4.0 ± 0.6 at 40 min postdive due to decreases in heart rate and stroke volume. This study shows that a single open sea dive may be associated with right heart overload due to increased pressure in the pulmonary artery.     

Hemodilution with liposome-encapsulated low-oxygen-affinity hemoglobin does not attenuate hypothermic cerebral ischemia in rats

Hypothermia decreases cerebral metabolism and increases hemoglobin oxygen affinity. A hypothesis that the reversal of increased oxygen affinity would further attenuate hypothermic cerebral ischemia was tested by evaluating the effects of liposome-encapsulated hemoglobin (LipoHb) with low oxygen affinity (P₅₀ = 40–50 mmHg) on hypothermic incomplete cerebral ischemia. Wistar rats were randomly assigned to one of the following two groups: (A) exchange transfusion with LipoHb solution (Hb = 6 g/dl) (LipoHb, n = 5), (B) no exchange transfusion (control, n = 5). After surface cooling to 22°C, forebrain ischemia was induced for 15 min by bilateral carotid artery occlusion combined with a decrease in the mean arterial pressure (MAP) to 40 mmHg. ³¹P-magnetic resonance spectroscopy was performed during ischemia and 45 min of reperfusion. After reperfusion, MAP was significantly higher in the control group than in the LipoHb group (P < 0.01), although there were no significant differences during ischemia. Intracellular pH and phosphocreatine (PCr) levels decreased during ischemia and returned to the preischemic level in both groups following reperfusion. The LipoHb group had a significantly larger decrease and smaller recovery in PCr than the control group (P < 0.0001). Althouth β-adenosine triphosphate decreased during ischemia in the LipoHb group, it increased in the control group (P < 0.0001). Inorganic phosphate (Pi) increased during ischemia and decreased to the normal value after reperfusion. The LipoHb group experienced a significantly larger production of Pi than the control group (P = 0.02). Hemodilution with high-P₅₀ LipoHb does not reduce ischemic energy depletion induced by hypothermic incomplete forebrain ischemia in rats.     

An electrical admittance based index of thoracic intracellular water during head-up tilt in humans

During 50° head-up tilt (HUT), the number of erythrocytes within the thorax has been shown to be reduced by approximately 25% and this level is retained during a maintained tilt, whilst that in the thigh increases by approximately 70%. To evaluate whether the electrical admittance of intracellular water (ICW) may be used to monitor this redistribution of red cells in humans, we determined the regional difference in the reciprocal value of the impedance at 1.5 and 100 kHz for the thorax (thorax_ICW) and for the leg (leg_ICW). In ten subjects all variables remained unchanged during head-down tilt but during HUT, presyncopal symptoms were induced in eight subjects after a mean of 27 (SEM 7) min as mean heart rate dropped from 85 (SEM 4) to 66 (SEM 3) beats · min⁻¹, mean arterial blood pressure from 80 (SEM 3) to 60 (SEM 5) mmHg, and mean oxygen saturation of venous blood from 76 (SEM 2)% to 73 (SEM 3)% (P < 0.05). The mean haematocrit increased from 50 (SEM 5)% to 52.5 (SEM 3.5)% (P < 0.01) and mean central venous pressure decreased during tilting (from a mean of 1 (SEM 1) to a mean of −1 (SEM 1) mmHg; P < 0.05) and returned to value at rest during the maintained tilt. Mean thoracic impedances increased by 7.0 (SEM 1.0) Ω (1.5 kHz) and 5.4 (SEM 1.2) Ω (100 kHz), and mean leg impedances decreased by 9.3 (SEM 1.2) Ω (1.5 kHz) and 3.1 (SEM 1.0) Ω (100 kHz) (P < 0.01). Mean thorax_ICW decreased at 40° HUT and remained reduced by 11 (SEM 2) S · 10⁻⁴ (P < 0.05) until the presyncopal symptoms developed, at which time it was lower by 16 (SEM 2) S · 10⁻⁴ (P < 0.01). Mean leg_ICW increased from 97 (SEM 15) to 99 (SEM 15) S · 10⁻⁴ (P=0.08) during HUT but decreased during maintained tilt (to 94 (SEM 15) S · 10⁻⁴; P < 0.05). The results suggested that during HUT, the difference in electrical admittance at a high and a low frequency current reflects the reduced number of red cells within the thorax. Accepted: 10 July 2000     

Arterial pressure-flow relations in the awake standing dog.

The transient circulatory changes following paced heart rate increase are reported from 133 trials with 6 unanesthetized dogs with chronically implanted monitoring devices for heart rate, cardiac output, aortic blood pressure, and mean right atrial pressure. In 62 trials with 2 of the dogs, pulmonary artery, and left ventricular end-diastolic pressure, as well as left ventricular dP/dt were also studied. The sequence of changes in pressures and flows is analyzed in terms of probable underlying mechanisms, particularly with respect to the nature of vascular resistances. The rise in aortic pressure and flow during the first 3 s of paced heart rate increase, before arterial stretch receptor reflexes become active, is more consistent with an effective downstream pressure of about 49 mmHg, presumably at the arteriolar level, than with an effective downstream pressure close to 0 mmHg at the right atrial level. In the pulmonary circulation where vascular reflex effects are less prominent, the pattern of pulmonary arterial pressure and flow for the entire 30 s of observation is consistent with an effective downstream pressure of 9 mmHg, presumably at the alveolar or pulmonary arteriolar level, rather than at the level of the left ventricular end-diastolic pressure.     

ANP gene expression in rat hearts during hypoxia

 It is unclear whether the increase in plasma atrial natriuretic peptide (ANP) concentration during hypoxia is due to direct, hypoxia-induced upregulation of ANP secretion in the heart, or to pressure overload of the right ventricle (RV) following hypoxia-induced pulmonary hypertension. To test the hypothesis that hypoxia leads to an early upregulation of the ANP gene, we examined the influence of acute and prolonged inspiratory hypoxia (6 h, 1 or 3 weeks) on the expression of ANP messenger ribonucleic acid (mRNA) in rat heart and compared the results with the expression of the ANP gene after acute pressure overload induced by experimental coarctation of the main pulmonary artery. As a molecular marker for hypertrophy we determined the ratio of α- and β-myosin gene expression. Hypoxia increased systolic RV pressure from 20.0 ± 1.6 mmHg to 27.8 ± 1.6 mmHg (P < 0.01) and 41.6 ± 2.1 mmHg (P < 0.05) after 1 and 3 weeks hypoxia respectively. The ANP plasma concentration did not change significantly after 6 h or 1 week: 232 ± 21 pg/ml (control), 246 ± 25 pg/ml (6 h), 268 ± 25 pg/ml (1 week), but increased significantly after 3 weeks hypoxia (446.8 ± 99.56 pg/ml; P < 0.05). ANP mRNA levels in different regions of the heart did not change after 6 h or 1 week hypoxia. After 3 weeks hypoxia ANP mRNA had increased 2.7-fold in the RV (P < 0.05), 4.2-fold in the left ventricle (LV, P < 0.05), 3.5-fold in the septum (S, P < 0.05) and about 1.4-fold in the right (n.s.) and left atrium (n.s.). Relative ventricular masses increased significantly only for the RV (190%, P < 0.05) during hypoxia. The β/α-myosin mRNA ratio did not change after 6 h hypoxia but, contrary to ANP gene expression, increased after just 1 week (6.1-fold in RV, 7.8-fold in LV, 6-fold in S; P < 0.05) and was more pronounced in the RV after 3 weeks (9.4-fold in RV, 7.6-fold in LV, 9.1-fold in S; P < 0.05). The increase in the β/α-myosin mRNA ratio in the LV contrasts with a lack of increase in relative ventricular mass. Acute pressure overload in the RV after pulmonary arterial banding significantly increased ANP-mRNA and the β/α-myosin mRNA ratio after 1 day in the RV. In the LV ANP mRNA was unchanged. The delayed upregulation of the ANP gene suggests that hypoxia per se is not a significant stimulus for ANP gene expression in the heart and that hypoxia-induced ANP-gene expression in the heart is regulated predominantly by the increase in RV afterload due to hypoxia-induced increased pulmonary pressure. The upregulation of ANP and β-myosin mRNA in the LV during chronic hypoxia has yet to be elucidated. Received: 5 November 1996 / Received after revision and accepted: 24 January 1997     

Difference in human cardiovascular response between upright and supine recovery from upright cycle exercise

Cardiovascular responses were examined in seven healthy male subjects during 10 min of recovery in the upright or supine position following 5 min of upright cycle exercise at 80% peak oxygen uptake. An initial rapid decrease in heart rate (f _c) during the early phase of recovery followed by much slower decrease was observed for both the upright and supine positions. The average f _c at the 10th min of recovery was significantly lower (P < 0.05) in the supine position than in the upright position, while they were both significantly greater than the corresponding pre-exercise levels (each P < 0.05). Accordingly, the amplitude of the high frequency (HF) component of R-R interval variability (by spectrum analysis) in both positions was reduced with a decrease in mean R-R interval, the relationship being expressed by a regression line – mean R-R interval = 0.006 × HF amplitude + 0.570 (r = 0.905, n = 28, P < 0.001). These results would suggest that the slower reduction in f _c following the initial rapid reduction in both positions is partly attributable to a retardation in the restoration of the activity of the cardiac parasympathetic nervous system. Post-exercise upright stroke volume (SV, by impedance cardiography) decreased gradually to just below the pre-exercise level, whereas post-exercise supine SV increased markedly to a level similar to that at rest before exercise. The resultant cardiac output (Q˙ _c) and the total peripheral vascular resistance (TPR) in the upright and supine positions returned gradually to their respective pre-exercise levels in the corresponding positions. At the 10th min of recovery, both average SV and Q˙ _c were significantly greater (each P < 0.005) in the supine than in the upright position, while average TPR was significantly lower (P < 0.05) in the supine than in the upright position. In contrast, immediately after exercise, mean blood pressure dropped markedly in both the supine and upright positions, and their levels at the 10th min of recovery were similar. Therefore we concluded that arterial blood pressure is maintained relatively constant through various compensatory mechanisms associated with f _c, SV, Q˙ _c, and TPR during rest and recovery in different body positions. Accepted: 4 September 1999     

Intra- and extracranial artery blood velocity during a sudden blood pressure decrease in humans

The intra- and extracerebral Doppler artery blood velocity responses to a 10-mmHg abrupt blood pressure (BP) decrease in ten healthy men were studied. This decrease was obtained using two cuffs placed over both thighs. First, cuffs were inflated to pressures greater than the arterial BP for 5 min. Next, they were deflated to 60 mmHg in order to prevent venous return from the legs. We obtained a decrease in mean arterial BP of from 101 (10) to 90 (10) mmHg [mean (SD), P < 0.01] without modifications in the heart rate [HR, 88 (14) beats min⁻¹]. Middle cerebral artery mean blood velocity (MCAmv) decreased immediately from 50 (10) to 42 (12) cm s⁻¹ (P < 0.05). Simultaneously, temporal superficial artery mean blood velocity (TSAmv) decreased from 11 (3) to 7 (2) cm s⁻¹ (P < 0.05) and common carotid artery blood flow (CCAbf ) decreased from 305 (23) to 233 (33) ml min⁻¹ (P < 0.05). After 5 s, MCAmv and CCAbf returned to baseline values, whereas TSAmv [8 (2) cm s⁻¹], mean arterial BP [86 (10) mmHg] remained low and HR increased [92 (12) beats min⁻¹]. TSAmv, BP and HR returned to baseline values in 1 min. These data confirm that cerebral blood flow (CBF) is very rapidly regulated but that blood flow in extracranial territories is not and that it follows the arterial BP changes. Accepted: 8 April 1997     

Neuromuscular adaptation during prolonged strength training, detraining and re-strength-training in middle-aged and elderly people

Effects of a 24-week strength training performed twice weekly (24 ST) (combined with explosive exercises) followed by either a 3-week detraining (3 DT) and a 21-week re-strength-training (21 RST) (experiment A) or by a 24-week detraining (24 DT) (experiment B) on neural activation of the agonist and antagonist leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris, maximal isometric and one repetition maximum (1-RM) strength and jumping (J) and walking (W) performances were examined. A group of middle-aged (M, 37–44 years, n=12) and elderly (E, 62–77, n=10) and another group of M (35–45, n=7) and E (63–78, n=7) served as subjects. In experiment A, the 1-RM increased substantially during 24 ST in M (27%, P < 0.001) and E (29%, P < 0.001) and in experiment B in M (29%, P < 0.001) and E (23%, P < 0.01). During 21 RST the 1-RM was increased by 5% at week 48 (P < 0.01) in M and 3% at week 41 in E (n.s., but P < 0.05 at week 34). In experiment A the integrated electromyogram (IEMG) of the vastus muscles in the 1-RM increased during 24 ST in both M (P < 0.05) and E (P < 0.001) and during 21 RST in M for the right (P < 0.05) and in E for both legs (P < 0.05). The biceps femoris co-activation during the 1-RM leg extension decreased during the first 8-week training in M (from 29 ± 5% to 25 ± 3%, n.s.) and especially in E (from 41 ± 11% to 32 ± 9%, P < 0.05). The CSA increased by 7% in M (P < 0.05) and by 7% in E (P < 0.001), and by 7% (n.s.) in M and by 3% in E (n.s.) during 24 ST periods. Increases of 18% (P < 0.001) and 12% (P < 0.05) in M and 22% (P < 0.001) and 26% (P < 0.05) in E occurred in J. W speed increased (P < 0.05) in both age groups. The only decrease during 3 DT was in maximal isometric force in M by 6% (P < 0.05) and by 4% (n.s.) in E. During 24 DT the CSA decreased in both age groups (P < 0.01), the 1-RM decreased by 6% (P < 0.05) in M and by 4% (P < 0.05) in E and isometric force by 12% (P < 0.001) in M and by 9% (P < 0.05) in E, respectively, while J and W remained unaltered. The strength gains were accompanied by increased maximal voluntary neural activation of the agonists in both age groups with reduced antagonist co-activation in the elderly during the initial training phases. Neural adaptation seemed to play a greater role than muscle hypertrophy. Short-term detraining led to only minor changes, while prolonged detraining resulted in muscle atrophy and decreased voluntary strength, but explosive jumping and walking actions in both age groups appeared to remain elevated for quite a long time by compensatory types of physical activities when performed on a regular basis. Accepted: 2 May 2000     

Influence of temperature on the distribution of blood in humans as assessed by electrical impedance

This study investigated whether ambient temperature influences the distribution of blood as indicated by electrical impedance. In ten supine humans, the room temperature was raised from 14 to 35°C. Skin temperature and blood flow on the thorax increased by 3.6 (SD 0.3)°C and 84 (SD 40)%, respectively, and by 9.8 (SD 1)°C and 115 (SD 45)%, respectively, on the extremities (P < 0.05). Cardiac output remained unchanged, ear temperature and heart rate became elevated, and the oesophageal temperature and mean arterial pressure decreased (P < 0.05). At five discrete frequencies (1.5, 5, 50, 100, 200 kHz) thoracic impedance was increased by 1.2 (SD 1) to 1.5 (SD 1) Ω (P < 0.05). In contrast, total body impedance was reduced by 16.4 (SD 5) Ω and leg impedance was reduced by 4.0 (SD 2) Ω, while an index of intracellular water within the thorax (the difference between the admittances at 100 kHz and 1.5 kHz) was decreased by 10 (SD 1) · 10⁻⁴ S (P < 0.05). The results would suggest that total body impedance is dominated by the impedance of the extremities. The increase in thoracic impedance and a decrease in leg impedance (as in total body impedance) could be explained by a redistribution of blood from the thorax to the extremities during heating. Such a translocation of blood was confirmed by a reduced impedance based index of intracellular water within the thorax. Accepted: 4 June 1999     

Thermoregulatory effects of three different types of head cooling in humans during a mild hyperthermia

Seven healthy young men participated in six trials with three different types of local cooling [cool air breathing (CAB), face skin cooling (FaC), and combined cooling (CoC)] in a warm environment for 90 min while either resting (operative temperature: T ₀ = 40°C, dew point temperature: T _dp = 15°C, air velocity: v _a = 0.3 m·s⁻¹) or exercising on a cycle ergometer with an external work load of 90 W (T ₀ = 36°C, T _dp = 15°C, v _a = 0.3 m·s⁻¹). Cool air (10°C) arrived at the entry point of the hood and/or the mask at a ventilation rate of 12 m · s⁻¹. Oesophageal temperature was not affected by any kind of cooling, while tympanic temperature was decreased at rest by both FaC and CoC [respectively −0.15 (0.06) and −0.09 (0.03)°C, P ≤ 0.05]. Mean skin temperature was decreased by FaC and CoC at rest [respectively −0.31 (0.07) and −0.27 (0.09)°C, P ≤ 0.05] and during exercise [respectively −0.64 (0.15) and −1.04 (0.22)°C, P ≤ 0.01]. CAB had no effect on skin temperatures. CoC and FaC reduced head skin temperature during both rest and work (P < 0.001) with no effect on the skin temperature of the rest of the body, except under CoC with exercise (P < 0.05). CAB did not influence local sweating. FaC, however, decreased the more profuse sweat rates (P ≤ 0.05) at rest, while CoC decreased all sweating rates at rest (P ≤ 0.05) and only the back, head and leg sweating rates during exercise (P ≤ 0.05). These results suggest that head skin cooling causes a reduction in heat strain, while CAB does not. This beneficial influence does not, however, appear to be the result of selective brain cooling. Tympanic temperature seems to be a good index of the core thermal inputs to the hypothalamic regulatory system, since variations in that parameter were associated with similarly directed variations in the sweating outputs. Accepted: 12 April 1999     

Cardiovascular effects of haemorrhagic shock in spleen intact and in splenectomized dogs

Cardiac performance was evaluated during haemorrhagic shock in 27 dogs with spleens intact, 24 splenectomized, and 23 splenectomized transfused dogs that were given a volume of packed red blood cells simulating splenic contraction. Contractile changes were evaluated by calculating dP/dt at 20 mmHg developed pressure (dP/dt DP20), and by relating stroke work to left ventricular end-diastolic volume measured by biplane cinefluorography. Although heart rate increased comparably during early shock, cardiac output, stroke volume, maximal dP/dt, dP/dt DP20, and arterial blood pressure decreased more in splenectomized and splenectomized transfused dogs than in those with spleens intact. During shock dP/dt DP20 was more depressed in the splenectomized and splenectomized transfused dogs than in those with spleens intact. In addition, an increase in left ventricular end-diastolic volume was accompanied by an increase in left ventricular stroke work in dogs with spleens intact. In contrast, stroke work remained depressed in both splenectomized groups despite increased left ventricular volume. Progressive acidosis and decreased left ventricular blood flow were similar in all dogs during haemorrhage. The greater reduction in left ventricular performance during haemorrhagic shock in the splenectomized and splenectomized transfused dogs was not related to excess lactate, changes in plasma volume, or red blood cell mass. Decreased left ventricular performance, despite improved ventricular filling, indicates greater cardiac dysfunction during haemorrhagic shock. This study suggests that, in dogs, the spleen maintains left ventricular performance during haemorrhage by mechanisms other than autotransfusion.     

Improved Left Ventricular Performance by the Transmission of Pulse Waves through the Pulmonary Vascular Bed

Piene , H. Improved left ventricular performance by the transmission of pulse waves through the pulmonary vascular bed. Acta physiol. scand. 1976. 98. 450–456. The influence on left ventricular performance of pulsewaves transmitted through the pulmonary vascular bed was studied in a cat lung preparation with the right heart bypassed by a pulsatile blood pump. The pump worked at a frequency slightly different from the intrinsic heart rate; transmitted pulse waves were thereby forced to arrive the left atrium at different phases of the left heart cycle. Slow fluctuations of left atrial pressure, left ventricular systolic pressure and left ventricular dP/dt were observed. Left ventricular systolic pressure and left ventricular dP/dt were maximum when the transmitted pulsewaves arrived left atrium just prior to the atrial contraction. The observed variation in left ventricular systolic pressure was found to be directly dependent on the magnitude of pulsatile hydraulic power transmitted to the left atrium.     

Alterations in the expression and activity of creatine kinase-M and mitochondrial creatine kinase subunits in skeletal muscle following prolonged intense exercise in rats

Creatine kinase (CK) isoenzymes are important structural and energy metabolism components in skeletal muscle. In this study, CK isoenzyme alterations were examined in male rats, with an 8% body mass weight attached to their tail. The rats were either forced to swim for 5 h (5S, n = 51), or were pre-trained for 8 days and then forced to swim for 5 h (T5S, n = 48). Rats were sacrificed either immediately (0 h PS), 3 h (3 h PS), or 48 h post-swimming (48 h PS). Serum CK was increased significantly (P < 0.01) 6.2- and 2.0-fold at 0 h PS following the 5S and T5S protocols, respectively. However, training (T5S protocol) significantly (P < 0.01) decreased CK release. Soleus and white gastrocnemius (WG) CK activity was significantly decreased following the 5S protocol (P < 0.05), but not following the T5S protocol. The CK-M activity of the soleus muscle was significantly (P < 0.05) decreased at 0 h PS following both the 5S and T5S protocols, and returned to control values at 3 h PS. The CK-M activity of the WG was significantly (P < 0.05) decreased at 0 h PS following the 5S protocol. Sarcomeric mitochondrial CK (sCK-Mit) was decreased significantly (P < 0.01) at 0 h PS (20%), 3 h PS (14%), 24 h PS (22%), and 48 h PS (15%) following the 5S protocol. However, sCK-Mit was decreased significantly (P < 0.01) only at 0 h PS (7%) following the T5S. The results of this study demonstrate that prolonged intense exercise causes a loss of skeletal muscle CK-M and sCK-Mit activity and that training prior to the prolonged intense exercise attenuates the exercise-induced CK-M and sCK-Mit loss in both red and white skeletal muscles. Accepted: 18 July 1999     

Serum protein alterations in dogs naturally infected with <Emphasis Type="Italic">Toxoplasma gondii</Emphasis>

We conducted this study to describe the serum electrophoretic pattern in dogs associated with the infection of Toxoplasma gondii (T. gondii). The serum protein pattern of 25 dogs with confirmed T. gondii infection and 15 clinically healthy dogs were evaluated using native polyacrylamide gel electrophoresis. Albumin, alpha-1 globulin, alpha-2 globulin, beta globulin, and gamma globulin bands were seen from the serum electrophoresis of infected and healthy dogs. Compared to the control group, significant decreases in the mean percentages of albumin (from 46.1 ± 7.2 to 40.8 ± 4.5%, P < 0.05), alpha-1 globulin (from 3.9 ± 0.4 to 0.8 ± 0.2%, P < 0.001), alpha-2 globulin (from 9.0 ± 0.4 to 8.3 ± 0.8%, P < 0.01), and beta globulin (from 18.4 ± 1.2 to 12.1 ± 0.6%, P < 0.001) in the infected group were determined. In contrast, gamma globulin fraction was significantly higher in infected dogs (38.1 ± 4.6%) than in control dogs (22.7 ± 7.2%; P < 0.001). Moreover, significant correlations were determined between the percentages of the albumin and gamma globulin fractions and liver enzyme tests including aspartate aminotransferase and alanine aminotransferase in infected dogs; however, no correlation was observed for the other protein fractions. In conclusion, marked alterations in serum protein pattern associated with strong modifications of serum protein concentrations are in accordance with the hepatic injury as affirmed by liver enzyme tests that were demonstrated in the canine toxoplasmosis. These findings showed that serum protein electrophoresis can be used in the diagnosis and prognosis of canine toxoplasmosis as a supplementary analysis in combination with serological, clinical, and laboratory findings of this disease.     

Gas exchange responses to continuous incremental cycle ergometry exercise in primary pulmonary hypertension in humans

In patients suffering from primary pulmonary hypertension (PPH), a raised pulmonary vascular resistance may limit the ability to increase pulmonary blood flow as work rate increases. We hypothesised that oxygen uptake (V˙O₂) may not rise appropriately with increasing work rate during incremental cardiopulmonary exercise tests. Nine PPH patients and nine normal subjects performed symptom-limited maximal continuous incremental cycle ergometry exercise. Mean peak V˙O₂ [1.00 (SD 0.22) compared to 2.58 (SD 0.64) l · min⁻¹] and mean V˙O₂ at lactic acidosis threshold [LAT, 0.73 (SD 0.17) compared to 1.46 (SD 0.21 · l) ml · min⁻¹] were much lower in patients than in normal subjects (both P < 0.01, two-way ANOVA with Tukey test). The mean rate of change of V˙O₂ with increasing work rate above the LAT [5.9 (SD 2.1) compared to 9.4 (SD 1.3) ml · min⁻¹ · W⁻¹, P < 0.01)] was also much lower in patients than in normal subjects [apparent δ efficiency 60.3 (SD 38.8)% in patients compared to 31.0 (SD 4.9)% in normal subjects]. The patients displayed lower mean values of end-tidal partial pressure of carbon dioxide than the normal subjects at peak exercise [29.7 (SD 6.8) compared to 42.4 (SD 5.8) mmHg, P < 0.01] and mean oxyhaemoglobin saturation [89.1 (SD 4.1) compared to 93.6 (SD 1.8)%, P < 0.05]. Mean ventilatory equivalents for CO₂ [49.3 (SD 11.4) compared to 35.0 (SD 7.3), P < 0.05] and O₂ [44.2 (SD 10.7) compared to 29.9 (SD 5.1), P < 0.05] were greater in patients than normal subjects. The sub-normal slopes for the V˙O₂-work-rate relationship above the LAT indicated severe impairment of the circulatory response to exercise in patients with PPH. The ventilatory abnormalities in PPH suggested that the lung had become an inefficient gas exchange organ because of impaired perfusion of the ventilated lung. Accepted: 17 April 2000     

Effects of platelet-rich plasma (PRP) on cutaneous regeneration and wound healing in dogs treated with dexamethasone

To evaluate the effects of platelet-rich plasma (PRP) on cutaneous regeneration and wound healing in dogs treated with dexamethasone, the present study was undertaken. Under general anesthesia, six full-thickness skin wounds were created on the back of five male adult dogs symmetrically. Left side wounds were left without any treatment, and right side wounds were treated topically with PRP jelly. Six days before creating the wounds, dogs received dexamethasone, 0.5 mg/kg IM, and every other day up to day 8 after wounding. For macroscopic evaluation, digital photographs were taken from wounds. In days 10, 17, and 24 after wounding, skin biopsies were taken from the center and corner of each wounds for hydroxyproline measurement and histopathological evaluation. No significant difference was seen in the percentage of wound contraction, epithelialization, and healing between test and control groups during the study (P > 0.05). There were no significant differences between median of hydroxyproline levels between left and right wounds in dogs treated with dexamethasone (P > 0.0.5). There were no significant differences between median of epithelialization, inflammatory cell infiltration, presence of dermal granulation tissue, fibroblast proliferation, arrangement of fibroblasts, collagen deposition, and collagen bundle formation scores, in the specimens of left and right wounds (P > 0.05). The results of the present study demonstrated that PRP did not have significant effects to promote cutaneous regeneration and wound healing in dogs treated with dexamethasone at least 16 days after last injection.