Central neural correlates of learned heart rate control during exercise: central command demystified

To identify the brain areas involved in central command, four monkeys were trained to attenuate the tachycardia of exercise while different brain sites affecting heart rate (HR) were simultaneously stimulated electrically. Among 24 brain sites located mostly in the limbic structures, we have identified four types of control systems that mediate cardiovascular and motor behavior during exercise. One system increases HR equivalently during both exercise and operantly controlled HR, whereas another increases HR during both tasks and abolishes operant HR control. In the third system, the effect of brain stimulation on HR is attenuated during exercise and during exercise with operantly controlled HR. The fourth system increases HR in both tasks, but its effect is significantly attenuated during operant HR control. We believe that this last system, which includes the mediodorsal nucleus, nucleus ventralis anterior, and cingulate cortex, plays a significant role in central command.     

Influence of parasympathetic dysfunction and hyperinsulinemia on the hemodynamic response to an isometric exercise in non-insulin-dependent diabetic patients

The handgrip test has long been used as a test for investigating cardiac autonomic neuropathy in diabetic patients. However, the factors involved in the hemodynamic response to the handgrip test have not been thoroughly studied. The aim of this study was to investigate blood pressure (BP) and heart rate (HR) responses to an isometric test in non-insulin-dependent diabetics (NIDDs) and to correlate the results with vagal function evaluated by three standardized tests and with plasma insulin levels. Fifty-five NIDDs, 35 of whom had one to three abnormal parasympathetic tests (PS+), were compared with 10 healthy control subjects. Fasting and postprandial plasma insulin levels were significantly higher in the PS+ than in the PS- patients. Resting HR correlated significantly with log fasting and postprandial insulin. In PS+ NIDDs, resting HR was significantly higher than in PS- patients. Age-matched comparisons also showed that resting systolic BP was significantly higher in PS+ patients than in controls. In PS- patients, the mean acceleration of HR was significantly higher than in the control group from the second to the fifth minute, and the BP response was also higher than in controls. These data suggest that (1) sympathetic response to an isometric exercise is increased in PS- NIDDs; (2) cardiac parasympathetic dysfunction is associated with a more severe insulin resistance; and (3) the subsequent higher plasma insulin level may contribute to the increase in resting HR and BP through sympathetic activation while limiting the hemodynamic response to an isometric exercise through its vasodilative effect.     

Peripheral and central inputs to the effort sense during cycling exercise

The relationships between some physical and physiological events, and perceived effort were studied at several equivalent work outputs (W) at two pedalling rates (30 and 60 rev-min-1). Subjects judged effort throughout a 4 min exercise bout. After 4 min at any W it was always more effortful to pedal at 30 rev-min-1 even though there were no differences in VE, VO2, or integrated electromyography per minute (IEMG-min-1) between pedalling rates. Effort was related to VO2 and IEMG-min-1 but it was more effortful to pedal at 30 rev-min-1. Effort was also related to pedal resistance and IEMG of single contractions but was influenced by pedalling rate after 4 min of exercise. At any resistance it was more effortful to pedal at 60 rev-min-1, however, when effort was plotted as a function of resistance after 15 s, there was virtually no effect of pedalling rate. The rate effect grows with time from the onset of exercise and appears to be related to the central signal to the effort sense. The interaction of peripheral and central signals suggests a model of the effort sense during exercise.     

Effects of isometric exercise on serum creatine phosphokinase activity

The effect of isometric exercise on serum creatinine phosphokinase (CPK) activity in 14 psychotic patients in remission and ten normal controls was studied. The increases in serum CPK activity at 18 and 42 hours after exercise were no significantly different in patients and controls. The postexercise serum CPK activities in the patients were significantly less than the peak serum CPK levels when they were psychotic. There were no significant correlations between postexercise serum CPK activity and preexercise or peak serum CPK activity in the patient group. It is unlikely that increased isometric muscle tension is a major causative factor in the increased serum CPK levels frequently found in psychotic patients.     

Direct vs indirect blood pressure at rest and during isometric exercise in normal subjects

Systolic and diastolic blood pressures were measured by intraarterial means and by auscultation. Comparisons were made with simultaneously determined intraarterial catheter and auscultation measurements. Five healthy males were measured at rest and during handgrip and deadlift isometric exercises, utilizing small and large muscle mass. The data suggest that indirect systolic blood pressure is highly correlated with the direct method at rest, during handgrip and deadlift (0.8, 0.9 and 0.91 respectively) isometric exercises. Indirect diastolic blood pressure correlates well with intraarterial at rest (0.7) and during the isometric handgrip bout which utilized small muscle mass (0.8). As for the deadlift manoeuvre, the correlation coefficients between the indirect and direct methods were low. These results suggest that when utilizing large muscle mass during isometric deadlift exercise, the indirect method is not valid for assessment of diastolic blood pressure.     

Effects of isometric exercise (handgrip) on the respiratory system]

Sixteen consecutive adult cases of Parinaud's syndrome are reviewed. Ten of the sixteen cases were due to brain stem infarction while four patients were suspected of harboring tumors. Parinaud's syndrome alone did not favor a diagnosis of tumor in the pineal region in this series. Associated neuroophthalmic findings are discussed.     

Function and production of nitric oxide in the coronary circulation of the conscious dog during exercise

This study determined the changes in NO production from the coronary circulation of the conscious dog during exercise. The role of endogenous NO as it relates to coronary flow, myocardial work, and metabolism was also studied. Mongrel dogs were chronically instrumented for measurements of coronary blood flow (CBF), ventricular and aortic pressure, and ventricular diameter, with catheters in the aorta and coronary sinus. Acute exercise (5 minutes at 3.6, 5.9, and 9.1 mph) was performed, and hemodynamic measurements and blood samples were taken at each exercise level. Nitro-L-arginine (NLA, 35 mg/kg IV) was given to block NO synthesis, and the exercise was repeated. Blood samples were analyzed for oxygen, plasma nitrate/nitrite (an index of NO), lactate, glucose, and free fatty acid (FFA) levels. Acute exercise caused significant elevations in NO production by the coronary circulation (46 +/- 23, 129 +/- 44, and 63 +/- 32 nmol/min at each speed respectively, P < .05). After NLA, there was no measurable NO production at rest or during exercise. Blockade of NO synthesis resulted in elevations in myocardial oxygen consumption and reductions in myocardial FFA consumption for comparable levels of CBF and cardiac work. The metabolic changes after NLA occurred in the absence of alterations in myocardial lactate or glucose consumptions. NO production by the coronary circulation is increased with exercise and blocked by NLA. The absence of NO in the coronary circulation during exercise does not affect levels of CBF, because it shifts the relationship between cardiac work and myocardial oxygen consumption, suggesting that endogenous NO modulates myocardial metabolism.     

Evaluation of the peripheral circulation during surgery by the difference between the central and peripheral temperature

The peripheral circulation during surgery was evaluated by the difference between rectal and sole deep temperature (RT-SDT) in 160 patients. Moreover it was investigated whether the peripheral circulation is influenced by the operation site, the method of anesthesia, the age of patient, the volume of infusion and blood loss. In many patients during intracranial, thoracic and upper abdominal surgeries, RT-SDT dissociated with time. But the change of RT-SDT varied with the anesthetic method. During upper abdominal surgery, RT-SDT tended to dissociate wtih the halothane (H) or enflurane (E)+N2O anesthesia and the wide dissociation was observed with fentanyl+droperidol+N2O anesthesia (NLA) on and after the 4th hour during the surgery. In contrast, RT-SDT continued to converge throughout the surgery in H or E+N2O+epidural anesthesia. The influence on RT-SDT of age, volume of infusion and blood loss, varied with the anesthetic method also. RT-SDT on the 4th hour during surgery correlated with the age of the patient, the volume of infusion in the H+N2O anesthesia, and with the volume of blood loss under NLA. The peripheral circulation during the surgery is affected seriously by anesthesia and the site as well as time of the operation. Therefore the anesthetic method should be selected in consideration of the type, length and site of operation. Some counter-measures should be taken in order to maintain good peripheral circulation in long operations.     

Effect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis

BACKGROUND/AIMS: Cirrhosis with portal hypertension is associated with changes in the splanchnic and systemic haemodynamics, and subsequent complications, such as bleeding from oesophageal varices, have led to the introduction of long-acting somatostatin analogues in the treatment of portal hypertension. However, reports on the splanchnic and systemic effects of octreotide are contradictory and therefore the aim of the present study was to assess the effects of continuous infusion of octreotide on central and systemic haemodynamics, portal pressures, and hepatic blood flow. METHODS: Thirteen patients with cirrhosis underwent liver vein catheterisation. Portal and arterial blood pressures were determined at baseline and 10, 30, and 50 min after a bolus injection of octreotide 100 micrograms, followed by continuous infusion of octreotide 100 micrograms/ h for 1 h. Hepatic blood flow, cardiac output, central and arterial blood volume, and central circulation time were determined at baseline and 50 min after the start of the octreotide infusion. RESULTS: The mean arterial blood pressure increased during the first 10 min (p < 0.0005), but returned to baseline after 50 min. The central and arterial blood volume (-16%, p < 0.005) and the central circulation time (-8%, p < 0.05) were significantly decreased after 50 min, whereas the cardiac output did not change significantly. The hepatic venous pressure gradient and the hepatic blood flow did not change significantly at any time after infusion of octreotide. CONCLUSIONS: Octreotide does not affect the portal pressure or hepatic blood flow, whereas it may further contract the central blood volume and thereby exert a potentially harmful effect on central hypovolaemia in patients with cirrhosis. However, these early effects do not exclude the possibility that administration of longacting somatostatin analogues over a longer period may have a beneficial effect.     

Influence of angiotensin II blockade during exercise in the heat

The effect of the blockade of the renin angiotensin system (RAS) on thermoregulatory, cardiovascular and renal function during moderate exercise in a hot [mean (SEM) 34.4 (0.1) degrees C] environment was evaluated. Six men and three women cycled at 60% peak oxygen uptake for 45 min following acute administration of a placebo (PLAC) or enalapril (ENAL), an angiotensin converting enzyme inhibitor (ACE-I). Resting mean arterial pressure (MAP) was reduced by ENAL, but the pressor response to exercise was unaffected [delta MAP = 7.8 (1.4)mmHg for both trials (P > 0.05)]. Peak esophageal temperature [T(es) = 38.7 (1.0) degrees C (PLAC) vs 38.4 (0.2) degrees C (ENAL)] and mean skin temperatures [Tsk = 36.5 (0.1) degrees C (PLAC) vs 36.6 (0.1) degrees C (ENAL)] were similar for both drug treatments during the exercise. Both aldosterone and plasma renin activity (PRA) increased five fold above resting values during exercise; however, only the PRA response [16.7 (3.2) ng angiotensin I (Ang I).ml-1.h-1 (ENAL) vs 7.4 (1.2)ng Ang I.ml-1.h-1 (PLAC)] was significantly altered by ENAL treatment (P < 0.05). Urine flow, sodium excretion and glomerular filtration rates, determined from creatinine clearance, were similarly reduced following exercise for both ENAL and PLAC treatments. These results suggest acute administration (5 mg) of ACE-I does not impair thermoregulatory, cardiovascular or renal responses during moderate exercise in the heat.     

Influence of chronic undernutrition on oxygen consumption of rats during exercise

The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone, and HgCl2 plus DTT. UN injected alone produced azotemia, decreased creatinine clearance, and rising fractional sodium excretion over the 48 hr of study. These effects of UN on renal function were not observed when DTT was administered 30 min after UN injection. Qualitatively similar results were obtained with HgCl2-induced acute renal failure. Groups of rats were killed at 6 hr after UN plus DTT, HgCl2 alone, or HgCl2 plus DTT; and determinations of plasma renin activity (PRA) and renin activities of the superficial and deep juxtaglomerular apparatus (JGA) were performed. PRA's and JGA renins were increased in animals receiving either UN or HgCl2 alone, but not in the rats receiving both DTT and UN or HgCl2. The effect of DTT on distribution of 203Hg was also examined. Treatment with DTT did not alter the renal accumulation of 203Hg, suggesting that this agent does not act by limiting renal exposure to the heavy metals. Thus, DTT ameliorates the course of heavy metal-induced ARF, and this effect is associated with prevention of heavy metal-induced alterations in sodium excretion and renin-angiotensin system activity.     

Systolic time intervals during isometric exercise in supine position should be corrected also for arterial pressure

In this paper we have studied the relationship between the systolic time intervals (STI) and the heart rate (HR) and systolic arterial pressure (SAP) in a group of 24 healthy subjects at three different effort levels during an isometric exercise in supine position and in basal conditions. We observed a decrease of the non corrected STI values during the exercise. Then we corrected STI using the regression equations obtained by plotting STI values versus the corresponding HR values at rest and during the exercise. We showed an increase of corrected left ventricular ejection time (LVET) during the whole exercise, and an increase of corrected total electromechanical systole (QS2c) at 50% effort level and then a return to the basal values. We also derived the multiple regression equations correlating QS2 and LVET with HR and SAP. Notwithstanding these equations show a significant positive correlation between the two STI considered and SAP only at the maximum effort, we corrected LVET and QS2 values by these equations assuming that the relationship between these parameters exists also in basal conditions and during the remaining stages of the exercise. By this correction we found a decrease of LVETc and QS2c in accordance with hemodynamic data reported by other authors. We may conclude that it seems useful to correct the STI obtained during isometric exercise in supine position both for HR and SAP.     

Influence of posture and training on the endurance time of a low-level isometric contraction

Classically, the critical force of a muscle (the relative force below which an isometric contraction can be maintained for a very long time without fatigue) is comprised of between 15 and 20% of its maximum voluntary contraction (MVC). However, some authors believe that the value is below 10% MVC. If such is the case, signs that accompany the establishment of muscle fatigue (EMG changes, continuous increase in systolic blood pressure [SBP] and heart rate [HR]) would have to appear more rapidly and with a higher intensity if the muscle is already partially fatigued at the start of maintaining a contraction at 10% MVC. Twelve healthy untrained participants carried out two isometric contractions with the digit flexors: one (test A) began with a maximum contraction sustained for 4 min followed without interruption by a contraction at 10% MVC for 61 min; the other (test B) was a contraction maintained at 10% MVC for 65 min. For test B, after an initial increase of 4 bpm with respect to at rest, HR remained stable until the end of contraction, SBP progressively increased by 24 mm Hg in 28 min, then remained unchanged until the end, and there were no significant changes in EMG (absence of spectral deviation towards low frequencies). For test A, in spite of the initial maximum contraction, changes in the parameters being studied (total maintenance time, HR, SBP, EMG) during maintenance at 10% MVC were identical to those for test B. The results show that (1) when the number and intensity of the co-contractions are minimized by applying an appropriate posture, it is possible to sustain an isometric contraction at 10% MVC for at least 65 min without the appearance of signs of muscle fatigue; (2) the critical force of the digit flexors is higher than 10% MVC.     

Effects of isometric handgrip exercise on coronary sinus blood flow in idiopathic cardiomyopathy

Rabbit proximal straight tubules from superficial nephrons were perfused in vitro in order to elucidate the mechanism of fluid and bicarbonate absorption. Both processes were greatly inhibited when sodium was replaced in the perfusate and bath by other cations, when ouabain was added to the bath, or when potassium was removed from the bath. We infer that these experimental manipulations inhibit active sodium tranport, and that active sodium transport is a primary process leading to fluid and bicarbonate absorption. Fluid absorption also decreased (but only by 22 to 36%) when bicarbonate was replaced by chloride in the perfusate and bath or when acetazolamide (10(-3)M) was added, suggesting that fluid and sodium transport depend in part on bicarbonate. We infer that the links between fluid, sodiu, and bicarbonate transport are complex and involve at least two mechanisms: 1) a sodium for hydrogen ion exchange mechanism located in the brush border membrane and 2) the transepithelial concentration difference for bicarbonate, which results from its absorption and which acts as an additional driving force for fluid and sodium absorption. Finally, bicarbonate absorption was unaltered when chloride was replaced by nitrate in the perfusate and bath, suggesting that chloride is not necessary for acidification in this nephron segment.     

Muscular reflex and baroreflex influences on heart rate during isometric contractions

Isometric hindlimb contractions were induced in anaesthetised dogs by stimulation of appropriate spinal ventral roots. During such contractions there were appreciable reflex systemic pressor responses accompanied by small increases in heart rate. The heart rate responses during contractions were small because the primary cardioacceleratory reflexes from muscle were partly masked during contractions by opposing baroreceptor-cardiodepressor reflexes.     

Influence of physiologic hyperglucagonemia on basal and insulin-inhibited splanchnic glucose output in normal man

To evaluate the effects of physiologic hyperglucagonemia on splanchnic glucose output, glucagon was infused in a dose of 3 ng/kg per min to healthy subjects in the basal state and after splanchnic glucose output had been inhibited by an infusion of glucose (2 mg/kg per min). In the basal state, infusion of glucagon causing a 309 +/- 25 pg/ml rise in plasma concentration was accompanied by a rapid increase in splanchnic glucose output to values two to three times basal by 7-15 min. The rise in arterial blood glucose (0.5-1.5 mM) correlated directly with the increment in splanchnic glucose output. Despite continued glucagon infusion, and in the face of stable insulin levels, splanchnic glucose output declined after 22 min, returning to basal levels by 30-45 min. In the subjects initially receiving the glucose infusion, arterial insulin concentration rose by 5-12 muU/ml, while splanchnic glucose output fell by 85-100%. Infusion of glucagon causing an increment in plasma glucagon concentration of 272 +/- 30 pg/ml reversed the inhibition in splanchnic glucose production within 5 min. Splanchnic glucose output reached a peak increment 60% above basal levels at 10 min, and subsequently declined to levels 20-25% below basal at 30-45 min. These findings provide direct evidence that physiologic increments in plasma glucagon stimulate splanchnic glucose output in the basal state and reverse insulin-mediated inhibition of splanchnic glucose production in normal man. The transient nature of the stimulatory effect of glucagon on splanchnic glucose output suggests the rapid development of inhibition or reversal of glucagon action. This inhibition does not appear to depend on increased insulin secretio.     

Influence of afferent feedback on isometric fine force resolution in humans

The infection of cultured endothelial cells with human cytomegalovirus (HCMV) is generally limited to less than 10% of the cells in contrast to HCMV infection of fibroblasts, where essentially all cells can be infected. It is known that HCMV infection influences a number of signal transduction pathways of infected cells. We therefore questioned whether, conversely, the infectivity of human umbilical vein endothelial cells could be influenced by the deliberate activation of these pathways. When endothelial cells were treated prior to infection with phorbol myristoyl acetate, an activator of protein kinase C, the number of HCMV-positive cells increased two to three times. On the other hand, pretreatment of the cells with RO 31-8220, a specific protein kinase C inhibitor, or with staurosporine, a general protein kinase inhibitor, resulted in a decreased infection level and in abolishment of the PMA-induced effect. Pretreatment with the protein phosphatase inhibitor, okadaic acid, caused a slight increase in infectivity, whereas pretreatment with the protein tyrosine kinase inhibitor, genistein, was without effect. Furthermore, neither forskolin and ilomedine, compounds known to activate the endothelial adenylate cyclase, nor the calcium ionophore A23187 were able to influence HCMV infectivity. It is concluded that: (a) the HCMV infection level of unstimulated endothelial cells is influenced by the basal level of protein kinase C; and (b) stimulation of protein kinase C prior to infection results in an increase of infection by HCMV.     

Effects of intraabdominally insufflated carbon dioxide and elevated intraabdominal pressure on splanchnic circulation: an experimental study in pigs

Scimitar-horned oryx sperm function was studied using protocols developed for domestic cattle. Objectives were to assess sperm 1) viability and motility in vitro over time, 2) capacitation in heparin- or calcium-supplemented medium, and 3) function in an in vitro fertilization system using heterologous (domestic cow) oocytes. Seminal aliquots were washed, and sperm were resuspended in 1) Talp with 5% fetal calf serum (TALP), 2) TALP + 10 microM heparin, 3) TALP + 20 microM heparin, and 4) TALP + 10 mM CaCl. At 0, 3, and 6 h, aliquots were evaluated for sperm motility, viability (using Hoechst 33258), and ability to acrosome-react when exposed to lysophosphatidylcholine (LC). Sperm function was assessed by evaluating fertilization and embryo development after coculture of in vitro-matured domestic cow oocytes with oryx sperm. Overall mean percentages of motile and viable sperm remained high at 6 h (> 60% and > 70%, respectively). Fewer (p < 0.05) sperm incubated in TALP + 10 microM heparin for 6 h contained intact acrosomes after exposure to LC, but there were no differences between LC and control samples after incubation in TALP without heparin. LC-treated sperm in TALP + 10 mM CaCl contained fewer (p < 0.05) intact acrosomes at 3 and 6 h (52.6% and 31.2%, respectively) than paired controls (83.6% and 70.0%, respectively). Oryx sperm from all males were capable of fertilizing cow oocytes (range 17 of 26 [65.4%] to 25 of 26 [96.2%]). Of the 55 2-cell embryos produced, 34 (61.8%) developed to > or = 8 cells. Of the 24 uncleaved oocytes, 7 (29.2%) were polyspermic. These data demonstrate that processed sperm from the endangered scimitar-horned oryx remain vigorous in vitro for at least 6 h. Capacitation can be induced using cattle sperm-processing techniques, with sperm appearing most responsive to elevated CaCl concentrations. Most interesting was the successful production and development of hybrid embryos after coincubation of oryx sperm with cow oocytes, suggesting that the two bovid species have similar fertilization mechanisms.