Hematorheology during deep hypothermia.

Hematologic and rheologic changes related to pure surface hypothermia procedures and procedures combining surface cooling and perfusion rewarming were studied in 16 dogs. White blood cell (WBC) and platelet counts decreased with surface cooling to about 20% of control and returned to control following surface rewarming. WBC and platelet counts returned to 80 and 50% of control depending on whether perfusion rewarming was stopped at 30 or 35 °C, respectively. Hemoconcentration was avoided during cooling with low molecular weight dextran hemodilution that was also in part responsible for a 33% decline in plasma proteins. Blood cooled in vitro and in vivo was studied by cone-plate viscometry and the viscosity noted to increase significantly as a function of decreased temperature. Computer analysis revealed that variations in temperature accounted for 75% of the variations in viscosity and variations in hematocrit contributed only 8%. An empiric formula was constructed that employs preoperative hematocrit and projected temperature to predict viscosity changes during cooling. The clinical relevance of hematologic and rheologic alterations during surface and combined hypothermia procedures was discussed.     

On the elastic properties of arteries

A new coefficient of elasticity is proposed that relates to the elastic state of the blood vessels. This measure is proposed as a result of the realization, from personal experience as well as from the international literature, of the difficulty in measuring the thickness of the blood vessels in vivo with acceptable precision. The measurement of E being dependent on the measurement of the thickness of the vessels becomes a highly unreliable proposition. Its relation to E (Young modulus) and to the pulse wave velocity (PWV) is established. We give three examples showing how the proposed coefficient can be measured.     

Serum enzyme levels during experimental hypothermia in man.

Deep surgical and accidental hypothermia cause elevations in serum enzyme levels, probably because of ultrastructural cell damage. Many variables hinder work on this problem in the clinical situation and the mechanism is obscure. Accordingly, enzymes and other physiological parameters were monitored in four subjects cooled four times, under controlled conditions in the laboratory, to a mean auditory canal temperature of 35.0 degrees C. Mild hypovolaemia and acidosis is occurred. Serum enzyme levels did not change significantly and it is concluded that elevations due to hypothermia cannot be studied in laboratory experiments on healthy volunteers who can only safely be cooled to 35 degrees C.     

Intrinsic properties of pharyngeal and diaphragmatic respiratory motoneurons and muscles.

Breathing is a complex act requiring the coordinated activity of multiple groups of muscles. Thoracic and abdominal respiratory muscles expand and contract the lungs, whereas pharyngeal and laryngeal respiratory muscles maintain upper airway patency and regulate upper airway resistance. An appreciation of the importance of the latter muscle group in maintaining ventilatory homeostasis and in the pathophysiology of sleep apnea has led to extensive studies examining the neural regulation of pharyngeal dilator muscles. The present review examines the role of heterogeneity in motoneuron and muscle properties in determining the diversity in the electrical and mechanical behaviors of thoracic compared with pharyngeal muscle groups. Specifically, phrenic and hypoglossal motoneuron electrophysiological properties influence whether and the extent to which these neurons will fire in response to a given synaptic input arising from chemo- and mechanoreceptors and from respiratory and nonrespiratory pattern generators. Furthermore, thoracic and pharyngeal muscle properties determine the mechanical response to motoneuronal activity, including the speed of contraction, relationships between motoneuron firing frequency and force production, and whether force is maintained during repetitive activation. Heterogeneity in the functional capabilities of these motoneurons and muscles is in turn determined by diversity of their structural and biochemical properties. Thus, intrinsic properties of respiratory motoneurons and muscles act in concert with neuronal drives in defining the complex electrical and mechanical behavior of pharyngeal and thoracic respiratory motor systems.     

Cardiac arrhythmias during rewarming of patients with accidental hypothermia.

Accidental hypothermia has a high mortality and is associated with cardiac arrhythmias. To determine the incidence of arrhythmias and their importance 22 patients with accidental hypothermia (core temperature less than 35 degrees C) were studied by 12 lead electrocardiography and continuous recording of cardiac rhythm. Although 14 of the patients died (64%), only six died while hypothermic. Prolongation of the Q-T interval and the presence of J waves were related to the severity of the hypothermia. Supraventricular arrhythmias, including atrial fibrillation, were common (nine cases) and benign. Ventricular extrasystoles were also common (10 cases), but ventricular tachycardia or fibrillation did not occur during rewarming. In eight patients who died while being monitored the terminal rhythm was asystole. There was no correlation between the severity of hypothermia or the rate of rewarming and the clinical outcome. In the absence of malignant arrhythmias there is no indication for using prophylactic antiarrhythmic treatment in patients with accidental hypothermia. The presence or absence of severe underlying disease is the main determinant of prognosis.     

Intrinsic autonomic innervation of the stomach during aging

In the senescence the cholinergic network of the basal and interglandular lamina propria and of the muscularis mucosae and submucosa of the gastric wall undergoes small modifications, while the adrenergic innervation decreases severely in the muscularis mucosae and in the interglandular tissue. Having regard to this adrenergic failure we note histochemically a rupture of the cholinergic/adrenergic balance in favour of the cholinergic innervation. These modifications disturb the gastrointestinal motility but their influence on the secretory reflex has to be demonstrated.     

Intrinsic cytosolic calcium buffering properties of single rat cardiac myocytes.

Intracellular passive Ca2+, buffering was measured in voltage-clamped rat ventricular myocytes. Cells were loaded with indo-1 (K+ salt) to an estimated cytosolic concentration of 44 +/- 5 microM (Mean +/- SEM, n = 5), and accessible cell volume was estimated to be 24.5 +/- 3.6 pl. Ca2+ transport by the sarcoplasmic reticulum (SR) Ca-ATPase and sarcolemmal Na-Ca exchange was inhibited by treatment with thapsigargin and Na-free solutions, respectively. Extracellular [Ca2+] was maintained at 10 mM and, in some experiments, the mitochondrial uncoupler "1799" was used to assess the degree of mitochondrial Ca2+ uptake. To perform single cell titrations, intracellular Ca2+ ([Ca2+]i) was increased progressively by a train of depolarizing voltage clamp pulses from -40 to +10 mV. The total Ca2+ gain with each pulse was calculated by integration of the Ca current and then analyzed as a function of the rapid change in [Ca2+]i during the pulse. In the range of [Ca2+]i from 0.1 to 2 microM, overall cell buffering was well described as a single lumped Michaelis-Menten type species with an apparent dissociation constant, KD, of of 0.63 +/- 0.07 microM (n = 5) and a binding capacity, Bmax, of 162 +/- 15 mumol/l cell H2O. Correction for buffering attributable to cytosolic indo-1 gives intrinsic cytosolic Ca2+ buffering parameters of KD = 0.96 +/- 0.18 microM and Bmax = 123 +/- 18 mumol/l cell H2O. The fast Ca2+ buffering measured in this manner agrees reasonably with the characteristics of known rapid Ca buffers (e.g., troponin C, calmodulin, and SR Ca-ATPase), but is only about half of the total Ca2+ buffering measured at equilibrium. Inclusion of slow Ca buffers such as the Ca/Mg sites on troponin C and myosin can account for the differences between fast Ca2+ buffering in phase with the Ca current measured in the present experiments and equilibrium Ca2+ buffering. The present data indicate that a rapid rise of [Ca2+]i from 0.1 to 1 microM during a contraction requires approximately 50 microM Ca2+ to be added to the cytosol.     

Neurohormonal alteration of integrative properties of the cardiac ganglion of the lobster Homarus americanus.

The spontaneous burst discharges of isolated lobster (Homarus americanus) cardiac ganglia were recorded with a spaced array of electrodes. Small regions (less than 1 mm) of the ganglion were exposed to the cardioexcitor neurohormone in extracts of pericardial organs (XPO) or to 10(-5) M 5-hydroxytryptamine (5HT). All axons were excited (increased mean firing frequency, f) by both substances, but only by applications in the region between the soma (but excluding it) and proximal site of impulse initiation. Units not so exposed changed their f relatively little despite f increases of as much as threefold in exposed units and changes in burst rate and overall length. Regularity and grouping of all impulse activity into bursts was never disturbed. 5HT increases burst rate at any point of application. The increases are larger if small cells are affected than if only large cells are exposed. Burst length decreases except when the pacemaker is affected. In contrast, XPO affects neither burst rate or length unless small cells are affected. Length is increased if non-pacemaker small cells are affected; both rate and length increase if the pacemaker is affected. The pacemaker usually exhibits an f of intermediate value. Rate changes are not simply related to its f. A small cell can "burst" in the absence of impulses from any other cells. XPO may enhance endogenous "driver potentials," while 5HT may excite by depolarizing at limited sites.     

Changes in contractile properties and neuromuscular propagation evaluated by simultaneous mechanomyogram and electromyogram during experimentally induced hypothermia.

The present study examined, whether or not mechanomyogram (MMG) amplitude and frequency component could reflect the contractile properties of the triceps surae muscles, composed of relatively slow soleus (SOL) and fast medial gastrocnemius (MG), during experimentally induced hypothermia condition. In eight male subjects, lying in prone position, supramaximal single twitch and repetitive electrical stimulations at 10 Hz were applied at the intramuscular temperatures of control (34 degrees C), 15, 20, and 25 degrees C, respectively. The hypothermia induced substantial reduction in muscle contractile properties, e.g. prolonged twitch contraction and half relaxation times, resulted in a highly significant reduction in the fluctuation of force signal during the repetitive stimulations. These changes were almost mirrored by the similar and significant reductions in the MMG amplitude in both SOL and MG. Power spectrum analysis revealed that peak frequency components of MMG and fluctuation of force were almost matched with the applied stimulation frequencies, independent of the temperature condition. These results strongly suggest that MMG analysis could be employed to study muscle contractile properties varying across different physiological conditions.     

Intrinsic contractile properties of the crucian carp (Carassius carassius) heart during anoxic and acidotic stress

The crucian carp (Carassius carassius) seems unique among vertebrates in its ability to maintain cardiac performance during prolonged anoxia. We investigated whether this phenomenon arises in part from a myocardium tolerant to severe acidosis or because the anoxic crucian carp heart may not experience a severe extracellular acidosis due to the fish's ability to convert lactate to ethanol. Spontaneously contracting heart preparations from cold-acclimated (6-8°C) carp were exposed (at 6.5°C) to graded or ungraded levels of acidosis under normoxic or anoxic conditions and intrinsic contractile performance was assessed. Our results clearly show that the carp heart is tolerant of acidosis as long as oxygen is available. However, heart rate and contraction kinetics of anoxic hearts were severely impaired when extracellular pH was decreased below 7.4. Nevertheless, the crucian carp heart was capable of recovering intrinsic contractile performance upon reoxygenation regardless of the severity of the anoxic + acidotic insult. Finally, we show that increased adrenergic stimulation can ameliorate, to a degree, the negative effects of severe acidosis on the intrinsic contractile properties of the anoxic crucian carp heart. Combined, these findings indicate an avoidance of severe extracellular acidosis and adrenergic stimulation are two important factors protecting the intrinsic contractile properties of the crucian carp heart during prolonged anoxia, and thus likely facilitate the ability of the anoxic crucian carp to maintain cardiac pumping.     

Inhibition of shivering during restraint hypothermia

Restraint hypothermia has often been described, but its cause has never been clarified. We hypothesized that it might be due to a suppression of shivering thermogenesis. Thus, we restrained conscious rats in an ambient temperature of 2 degrees C while measuring rectal (Tre) and tail skin temperatures, metabolic rate (MR), and shivering activity. When rats were cold exposed but not restrained, Tre fell 1.4 +/- 0.2 degrees C (SE) during the 1st h. When these same rats were restrained, Tre fell at a rate of 6.5 +/- 0.2 degrees C/h. MR averaged 15.7 +/- 1.4 W/kg for the unrestrained rats, but it averaged only 9.0 +/- 1.1 W/kg for the restrained rats. The restrained rats showed no signs of shivering. The animals were then subjected to a restraint adaptation regimen and then reexposed to cold. Restraint now produced a fall in Tre of only 2.6 +/- 0.7 degrees C/h. The animals shivered and generated an MR of 15.8 +/- 0.9 W/kg. Naive rats became hypothermic because restraint suppressed shivering activity. However, adapted rats continued to shiver and remained normothermic. We suggest that a stressful or threatening situation, such as restraint for a naive rat, inhibits shivering and leads to hypothermia in a cold environment. This would not occur in adapted rats because restraint is no longer stressful.     

Specific alteration of the 30S ribosomal subunits of Bacillus subtilis during sporulation.

Active 30S ribosomal subunits were isolated from vegetative and sporulating cells of Bacillus subtilis. Both subunits were able to function in polyuridylic acid of phage phie messenger ribonucleic acid-dependent protein synthesis in vitro. The sporulation 30S subunits were highly active in polyuridylic acid-dependent polyphenylalanine synthesis but showed a reduced activity in the presence of natural messenger ribonucleic acid as compared with their vegetative counter-parts. The reduced activity was independent of the source of 50S particles and initiation factors (vegetative or sporulation). The alteration of the 30S sporulation subunits appears to be related to the sporulation process, since the same subunits isolated from stationary-phase cells of an asporogenic mutant did not show any impairment in protein synthesis in vitro.     

Quantifying the Reconfiguration of Intrinsic Networks during Working Memory

Rapid, flexible reconfiguration of connections across brain regions is thought to underlie successful cognitive control. Two intrinsic networks in particular, the cingulo-opercular (CO) and fronto-parietal (FP), are thought to underlie two operations critical for cognitive control: task-set maintenance/tonic alertness and adaptive, trial-by-trial updating. Using functional magnetic resonance imaging, we directly tested whether the functional connectivity of the CO and FP networks was related to cognitive demands and behavior. We focused on working memory because of evidence that during working memory tasks the entire brain becomes more integrated. When specifically probing the CO and FP cognitive control networks, we found that individual regions of both intrinsic networks were active during working memory and, as expected, integration across the two networks increased during task blocks that required cognitive control. Crucially, increased integration between each of the cognitive control networks and a task-related, non-cognitive control network (the hand somatosensory-motor network; SM) was related to increased accuracy. This implies that dynamic reconfiguration of the CO and FP networks so as to increase their inter-network communication underlies successful working memory.