Effect of active forced air warming during the first hour after anesthesia induction and intraoperation avoids hypothermia in elderly patients.

BACKGROUND: The study aimed at exploring an optimal temperature model of forced air warming during the first hour after induction and intraoperation to prevent hyperthermia for elderly patients undergoing laparoscopic abdominal surgery. METHODS: There were 218 patients that were randomly divided into 3 groups warmed with a forced-air warmer during surgery: Group L (intraoperative warming set to 38 °C, n = 63), Group H (intraoperative warming set to 42 °C, n = 65) and Group LH (intraoperative warming set to 42 °C for the first hour then set to 38 °C, n = 65). Core temperature in the preoperative room and PACU was measured by a tympanic membrane thermometer and in the operation room, a nasopharyngeal temperature probe was recorded. The rate of perioperative hypothermia, defined as a reduction in body temperature to < 36 °C was recorded as the primary outcome. Intraoperative anesthetic dosage, recovery time, adverse events, thermal comfort and satisfaction score were measured as secondary outcome. RESULTS: The incidence of intraoperative and postoperative hypothermia was significantly lower in Group LH and Group H than Group L (18.75 and 15.62% vs 44.44%, P<0.001; 4.69 and 4.69% vs 20.63%, P<.05). Anesthetic dosage of rocuronium was lower in Group L than other two groups, with the opposite result of recovery time. The number of patients with shivering was higher in Group L but sweating was higher in Group H. Both of the thermal comfort and satisfaction score was highest in Group LH. CONCLUSION: A temperature pattern of forced air warming set at 42 °C during the first hour after anesthesia induction and maintained with 38 °C was a suitable choice for elderly patients undergoing laparoscopic abdominal surgery lasting for more than 120 min. TRIAL REGISTRATION: Chictr.org.cn ChiCTR-2,100,053,211.

Soluble thrombomodulin ameliorates aberrant hemostasis after rewarming in a rat accidental hypothermia model.

BACKGROUND: Accidental hypothermia (AH) sometimes leads to coagulation disorder, especially in severe AH. We previously demonstrated that intrasplenic platelet activation caused aberrant hemostasis and thrombus formation after rewarming in a murine AH model. However, no study has focused on the appropriate management of platelets causing coagulation activation after rewarming of AH. We investigated whether or not recombinant soluble thrombomodulin (rTM) can suppress thrombosis formation after rewarming using a rat AH model. METHODS: Wistar rats were exposed to an ambient temperature of -20 °C under general anesthesia until their rectal temperature decreased to 26 °C. The Hypo group rats (n = 5) were immediately euthanized, while the Hypo/Re group (n = 5) and rTM group rats (n = 5), which were administered rTM (1 mg/kg) via the tail vein, were rewarmed until the rectal temperature returned to 34 °C and then euthanized 6 h later. Tissue and blood samples were collected from all rats for histopathological and coagulation analyses at euthanasia. RESULTS: There was no significant change in the D-dimer level in the Hypo group rats, while the D-dimer level was significantly elevated at 6 h after rewarming in the Hypo/Re group rats (P = 0.015), and histopathology detected both fibrin and platelets in the renal glomerulus. However, the rTM group rats did not show any elevation of the D-dimer levels at 6 h after rewarming, and no fibrin was noted on histopathology. CONCLUSIONS: rTM may be useful as an appropriate anticoagulant in cases of aberrant hemostasis after rewarming of AH.

Left Ventricular Function Changes Induced by Moderate Hypothermia Are Rapidly Reversed After Rewarming-A Clinical Study.

OBJECTIVES: Targeted temperature management (32-36°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental results, we hypothesized that hypothermia would reversibly impair diastolic function with less tolerance to increased heart rate in patients with uninsulted hearts. DESIGN: Prospective clinical study, from June 2015 to May 2018. SETTING: Cardiothoracic surgery operation room, Oslo University Hospital. PATIENTS: Twenty patients with left ventricular ejection fraction greater than 55%, undergoing ascending aorta graft-replacement connected to cardiopulmonary bypass were included. INTERVENTIONS: Left ventricular function was assessed during reduced cardiopulmonary bypass support at 36°C, 32°C prior to graft-replacement, and at 36°C postsurgery. Electrocardiogram, hemodynamic, and echocardiographic recordings were made at spontaneous heart rate and 90 beats per minute at comparable loading conditions. MEASUREMENTS AND MAIN RESULTS: Hypothermia decreased spontaneous heart rate, and R-R interval was prolonged (862 ± 170 to 1,156 ± 254 ms, p < 0.001). Although systolic and diastolic fractions of R-R interval were preserved (0.43 ± 0.07 and 0.57 ± 0.07), isovolumic relaxation time increased and diastolic filling time was shortened. Filling pattern changed from early to late filling. Systolic function was preserved with unchanged myocardial strain and stroke volume index, but cardiac index was reduced with maintained mixed venous oxygen saturation. At increased heart rate, systolic fraction exceeded diastolic fraction (0.53 ± 0.05 and 0.47 ± 0.05) with diastolic impairment. Strain and stroke volume index were reduced, the latter to 65% of stroke volume index at spontaneous heart rate. Cardiac index decreased, but mixed venous oxygen saturation was maintained. After rewarming, myocardial function was restored. CONCLUSIONS: In patients with normal left ventricular function, hypothermia impaired diastolic function. At increased heart rate, systolic function was subsequently reduced due to impeded filling. Changes in left ventricular function were rapidly reversed after rewarming.

Changes in breathing pattern during severe hypothermia and autoresuscitation from hypothermic respiratory arrest in anesthetized mice.

Some evidence suggests that both hypothermia and anesthesia can exert similar effects on metabolism and ventilation. This study examined the synergistic effects of anesthesia and hypothermia on ventilation in spontaneously breathing adult mice under three different conditions, that is, (1) pentobarbital group (n = 7) in which mice were anesthetized with intraperitoneal pentobarbital of 80 mg/kg, (2) sevoflurane-continued group (n = 7) in which mice were anesthetized with 1 MAC sevoflurane, and (3) sevoflurane-discontinued group (n = 7) in which sevoflurane was discontinued at a body temperature below 22˚C. We cooled mice in each group until breathing ceased and followed this with artificial rewarming while measuring changes in respiratory variables and heart rate. We found that the body temperature at which respiration arrested is much lower in the sevoflurane-discontinued group (13.8 ± 2.0˚C) than that in the sevoflurane-continued group (16.7 ± 1.2˚C) and the pentobarbital group (17.0 ± 1.4˚C). Upon rewarming, all animals in all three groups spontaneously recovered from respiratory arrest. There was a considerable difference in breathing patterns between sevoflurane-anesthetized mice and pentobarbital-anesthetized mice during progressive hypothermia in terms of changes in tidal volume and respiratory frequency. The changes in the respiratory pattern during rewarming are nearly mirrored images of the changes observed during cooling in all three groups. These observations indicate that adult mice are capable of autoresuscitation from hypothermic respiratory arrest and that anesthesia and hypothermia exert synergistic effects on the occurrence of respiratory arrest while the type of anesthetic affects the breathing pattern that occurs during progressive hypothermia leading to respiratory arrest.

Delta QRS distinguishes Ito -mediated J waves from pseudo J waves produced by conduction delay on body surface electrocardiographic.

BACKGROUND: On surface electrocardiographic (ECGs), it is difficult to differentiate Ito -mediated J waves, a repolarization phenomenon seen in J wave syndromes (JWS) from terminal QRS deflections that mimic J waves (pseudo J waves) in intraventricular conduction delay (IVCD), an abnormality in depolarization. We hypothesize that the difference between the "maximum QRS duration" inclusive of J point or terminal QRS deflections and the minimum QRS duration identified across a 12-lead ECG is significantly larger in Ito -mediated J waves, and can serve as a marker to make this distinction. METHODS: A retrospective analysis was performed on adults with ECGs consisting of one of the four following manifestations: J waves associated with hypothermia and early repolarization, and pseudo J waves associated with right bundle branch block (RBBB) and non-specific intraventricular conduction delay (NS-IVCD). All ECGs were assessed individually and the maximum and minimum discrete QRS deflections on 12-lead tracings, defined as "QRSmax " and QRSmin , were identified. The difference between "QRSmax " and QRSmin , designated as ∆QRS, was calculated and compared across the studied populations. RESULTS: A total of 60 patients consisting of 15 patients in each arm were included in the study. ΔQRS was significantly larger in the hypothermia and early repolarization groups, compared to RBBB and NS-IVCD (p < .0001), with the following mean ∆QRS: hypothermia 54.3 ± 13.7 ms, early repolarization pattern 47.3 ± 15.3 ms, RBBB 19.3 ± 6.5 ms, and NS-IVCD 16.0 ± 6.6 ms. CONCLUSION: ∆QRS may serve as a reliable ECG parameter for distinguishing Ito -mediated J waves from pseudo J waves produced by delayed intraventricular conduction.

Effects of rewarming with extracorporeal membrane oxygenation to restore oxygen transport and organ blood flow after hypothermic cardiac arrest in a porcine model.

We recently documented that cardiopulmonary resuscitation (CPR) generates the same level of cardiac output (CO) and mean arterial pressure (MAP) during both normothermia (38 °C) and hypothermia (27 °C). Furthermore, continuous CPR at 27 °C provides O2 delivery (DO2) to support aerobic metabolism throughout a 3-h period. The aim of the present study was to investigate the effects of extracorporeal membrane oxygenation (ECMO) rewarming to restore DO2 and organ blood flow after prolonged hypothermic cardiac arrest. Eight male pigs were anesthetized and immersion cooled to 27 °C. After induction of hypothermic cardiac arrest, CPR was started and continued for a 3-h period. Thereafter, the animals were rewarmed with ECMO. Organ blood flow was measured using microspheres. After cooling with spontaneous circulation to 27 °C, MAP and CO were initially reduced to 66 and 44% of baseline, respectively. By 15 min after the onset of CPR, there was a further reduction in MAP and CO to 42 and 25% of baseline, respectively, which remained unchanged throughout the rest of 3-h CPR. During CPR, DO2 and O2 uptake (V̇O2) fell to critical low levels, but the simultaneous small increase in lactate and a modest reduction in pH, indicated the presence of maintained aerobic metabolism. Rewarming with ECMO restored MAP, CO, DO2, and blood flow to the heart and to parts of the brain, whereas flow to kidneys, stomach, liver and spleen remained significantly reduced. CPR for 3-h at 27 °C with sustained lower levels of CO and MAP maintained aerobic metabolism sufficient to support DO2. Rewarming with ECMO restores blood flow to the heart and brain, and creates a "shockable" cardiac rhythm. Thus, like continuous CPR, ECMO rewarming plays a crucial role in "the chain of survival" when resuscitating victims of hypothermic cardiac arrest.

Naturally occurring hypothermia promotes survival in severe anaphylaxis.

Although hypothermia has received substantial attention as an indicator of severity in anaphylaxis, it has been neglected from the perspective of whether it could act as a disease-modifying factor in this condition. Here, the impact of naturally occurring (spontaneous) hypothermia on anaphylaxis was evaluated in a murine model of ovalbumin (OVA)-induced allergy. Nonextreme changes in the ambient temperature (Ta) were used to modulate the magnitude of spontaneous hypothermia. At a Ta of 24°C, challenge with OVA intraperitoneally or intravenously resulted in a rapid, transient fall in body core temperature, which reached its nadir 4-6°C below baseline in 30 min. This hypothermic response was largely attenuated when the mice were kept at a Ta of 34°C. The Ta-dependent attenuation of hypothermia resulted in a survival rate of only 30%, as opposed to survival of 100% in the condition that favored the development of hypothermia. The protective effect of hypothermia did not involve changes in the rate of mast cell degranulation, as assessed by the concentration of mast cell protease-1 in bodily fluids. On the other hand, hypothermia improved oxygenation of the brain and kidneys, as indicated by higher NAD+/NADH ratios. Therefore, it is plausible to propose that naturally occurring hypothermia makes organs more resistant to the anaphylactic insult.

Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia in mice.

The neural mechanisms of fear-associated thermoregulation remain unclear. Innate fear odor 2-methyl-2-thiazoline (2MT) elicits rapid hypothermia and elevated tail temperature, indicative of vasodilation-induced heat dissipation, in wild-type mice, but not in mice lacking Trpa1-the chemosensor for 2MT. Here we report that Trpa1-/- mice show diminished 2MT-evoked c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel) and nucleus of the solitary tract (NTS). Whereas tetanus toxin light chain-mediated inactivation of NTS-projecting PSTh neurons suppress, optogenetic activation of direct PSTh-rostral NTS pathway induces hypothermia and tail vasodilation. Furthermore, selective opto-stimulation of 2MT-activated, PSTh-projecting PBel neurons by capturing activated neuronal ensembles (CANE) causes hypothermia. Conversely, chemogenetic suppression of vGlut2+ neurons in PBel or PSTh, or PSTh-projecting PBel neurons attenuates 2MT-evoked hypothermia and tail vasodilation. These studies identify PSTh as a major thermoregulatory hub that connects PBel to NTS to mediate 2MT-evoked innate fear-associated hypothermia and tail vasodilation.

Central GABAA receptor mediates taurine-induced hypothermia and possibly reduces food intake in thermo-neutral chicks and regulates plasma metabolites in heat-exposed chicks.

The aim of this study was to examine the central action of taurine on body temperature and food intake in neonatal chicks under control thermoneutral temperature (CT) and high ambient temperature (HT). Intracerebroventricular injection of taurine caused dose-dependent hypothermia and reduced food intake under CT. The mRNA expression of the GABAA receptors, GABAAR-α1 and GABAAR-γ, but not that of GABABR, significantly decreased in the diencephalon after central injection of taurine. Subsequently, we found that picrotoxin, a GABAAR antagonist, attenuated taurine-induced hypothermia. Central taurine significantly decreased the brain concentrations of 3-methoxy-4-hydroxyphenylglycol, a major metabolite of norepinephrine; however, the concentrations of serotonin, dopamine, and the epinephrine metabolites, 3,4-hydroxyindoleacetic acid and homovanillic acid, were unchanged. Although hypothermia was not observed under HT after central injection of taurine, plasma glucose and uric acid levels were higher, and plasma sodium and calcium levels were lower, than those in chicks under CT. In conclusion, brain taurine may play a role in regulating body temperature and food intake in chicks through GABAAR. The changes in plasma metabolites under heat stress suggest that brain taurine may play an important role in maintaining homeostasis in chicks.

Pharmacological torpor prolongs rat survival in lethal normobaric hypoxia.

Resistance to hypoxia is one of the most prominent features of natural hibernation and is expected to be present in the pharmacological torpor (PT) that simulates hibernation. We studied resistance to lethal hypoxia (3.5% oxygen content) in rats under PT. To initiate PT, we used the previously developed pharmacological composition (PC) which, after a single intravenous injection, can induce a daily decrease in Tb by 7 °C-8 °C at the environmental temperature of 22 °C-23 °C. Half-survival (median) time of rats in lethal hypoxia was found to increase from 5 ± 0.8 min in anesthetized control rats to 150 ± 12 min in rats injected with PC, which is a 30-fold increase. Behavioral tests after PT and hypoxia, including the traveling distance, the number of rearing and grooming episodes, revealed that animal responses are significantly restored within a week. It is assumed that the discovered unprecedented resistance of artificially torpid rats to lethal hypoxia may open up broad prospects for the therapeutic use of PT for preconditioning to various damaging factors, treatment of diseases, and extend the so-called "golden hour" for lifesaving interventions.

Effect of Preoperative Oral Carbohydrate Loading on Body Temperature During Combined Spinal-Epidural Anesthesia for Elective Cesarean Delivery.

BACKGROUND: Intraoperative hypothermia is a common complication after neuraxial block in cesarean delivery. At least 1 animal study has found that carbohydrate loading can maintain the body temperature of rats during general anesthesia, but it is unclear whether carbohydrate loading is beneficial for body temperature maintenance in parturient women during combined spinal-epidural anesthesia (CSEA) for elective cesarean delivery. METHODS: Women undergoing elective cesarean delivery were randomized into a control group (group C), an oral carbohydrate group (group OC), or an oral placebo group (group OP), with 40 women in each group. Core body temperature (Tc) and body surface temperature (Ts) before and after cesarean delivery, changes in Tc (ΔTc) and Ts (ΔTs), and the incidence of side effects (eg, intraoperative shivering) were compared among the groups. RESULTS: The postoperative Tc (core body temperature after cesarean delivery [Tc2]) of group OC (36.48 [0.48]°C) was higher than those of group C (35.95 [0.55]°C; P < .001), and group OP (36.03 [0.49]°C; P = .001). The ΔTc (0.30 [0.39]°C) in group OC was significantly smaller than those in group C (0.73 [0.40]°C; P = .001) and group OP (0.63 [0.46]°C; P = .0048). CONCLUSIONS: Oral carbohydrate loading 2 hours before surgery facilitated body temperature maintenance during CSEA for elective cesarean delivery.

Plasmatic and cell-based enhancement by microparticles originated from platelets and endothelial cells under simulated in vitro conditions of a dilutional coagulopathy.

BACKGROUND: Aggressive fluid management and other external factors may lead to hypothermia, acidosis and hemodilution (defined as Lethal Triad, LT) contributing to a trauma-induced coagulopathy (TIC) that worsens patients' outcomes. Procoagulant microparticles (MP) are crucial players at the interface of cellular and plasmatic coagulation. However, their functions remain largely unexplored. This study aimed to characterize effects of MP subtypes and concentrations on functional coagulation under in vitro simulated conditions. METHODS: Blood from eleven volunteers were collected to simulate in vitro conditions of hemodilution (HD) and LT, respectively. HD was induced by replacing a blood volume of 33% by crystalloids and for LT, samples were further processed by reducing the temperature to 32 °C and lowering the pH to 6.8. MP were obtained either from platelet concentrates (platelet-derived MP, PDMP) or from cell culture (ECV304 cells for endothelial-derived MP, EDMP) by targeted stimulation. After introducing MP to in vitro conditions, we measured their concentration-dependent effects (1.000, 10.000 and 15.000 MP/µl blood) on coagulation compared to whole blood (WB). For each condition, coagulation was characterized by flow cytometric platelet activation and by quantification of fibrin clot propagation using Thrombodynamics® technology. RESULTS: MP originated from platelets and endothelial cells affected blood coagulation in a concentration-dependent manner. Particularly, high PDMP quantities (10.000 and 15.000 PDMP/µl blood) significantly induced platelet activation and fibrin clot growth and size in HD conditions. In LT conditions as well, only high PDMP concentration induced platelet activation, clot growth and size. In contrast, EDMP did not induce platelet activation, but resulted in enhanced formation of spontaneous clots, irrespective of simulated condition. With increasing EDMP concentration, the time until the onset of spontaneous clotting decreased in both HD and LT conditions. DISCUSSION: The study demonstrates an essential role of MP within the coagulation process under simulated coagulopathic conditions. PDMP affected platelets promoting clot formation likely by providing a surface enlargement. EDMP presumably affected clotting factors of the plasmatic coagulation resulting in an increased formation of spontaneous clots. CONCLUSION: Under simulated conditions of a dilutional coagulopathy, MP from different cellular origin indicate a divergent but both procoagulant mechanism within the coagulation process.

Selective-cerebral-hypothermia-induced neuroprotection against-focal cerebral ischemia/reperfusion injury is associated with an increase in SUMO2/3 conjugation.

Selective cerebral hypothermia is considered an effective treatment for neuronal injury after stroke and avoids the complications of general hypothermia. Several recent studies hanve suggested that SUMO2/3 conjugation occurs following cerebral ischemia/reperfusion (I/R) injury. However, the relationship between the cerebral protective effect of selective cerebral hypothermia and SUMO2/3 conjugation remains unclear. In this study, we investigated the effect of selective cerebral hypothermia on SUMO2/3 conjugation during focal cerebral I/R injury. A total of 140 Sprague-Dawley rats were divided into four groups. In the sham group, only the carotid artery was exposed. The endoluminal filament technique was used to induce middle cerebral artery occlusion in the other three groups. After 2 h of occlusion, the filaments were slowly removed to allow blood reperfusion in the I/R group. In the hypothermia (HT) group and normothermia (NT) group, normal saline at 4 °C and 37 °C, respectively , was perfused through the carotid artery, followed by the restoration of blood flow. The results of the modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining demonstrated that selective cerebral hypothermia significantly decreased I/R-induced neuronal injury (mNSS, n = 8, 24 h, HT (5.88 ± 2.36) vs. I/R (8.63 ± 3.38), P < 0.05. 48 h, HT (5.75 ± 2.25) vs. I/R (8.5 ± 2.88), P < 0.05. Cerebral infarct volume percentages, n = 5, HT (18.71 ± 2.13) vs. I/R (41.52 ± 2.90), P < 0.01. Cell apoptosis rate, n = 5, 24 h, HT (21.28 ± 2.61) vs. I/R (43.72 ± 4.30), P < 0.05. 48 h, HT (20.50 ± 2.53) vs. I/R (38.94 ± 2.93), P < 0.05). The expression of Ubc9 and conjugated SUMO2/3 proteins was increased at 24 and 48 h after reperfusion in the 3 non-sham groups, and hypothermia further upregulated the expression of Ubc9 and conjugated SUMO2/3 proteins in the HT group. The expression of SENP3 was increased in the NT group and I/R group, while it was decreased in the HT group at 24 and 48 h after reperfusion (Relative quantities, n = 5, Ubc9, 24 h, HT (2.44 ± 0.22) vs. I/R (1.55 ± 0.39), P < 0.05. 48 h, HT (2.69 ± 0.16) vs. I/R (2.25 ± 0.33), P < 0.05. SENP3, 24 h, HT (0.47 ± 0.15) vs. I/R (2.18 ± 0.43), P < 0.05. 48 h, HT (0.72 ± 0.06) vs. I/R (1.51 ± 0.19), P < 0.05. conjugated SUMO2/3 proteins, 24 h, HT (2.84 ± 0.24) vs. I/R (2.51 ± 0.20), P < 0.05. 48 h, HT (2.73 ± 0.13) vs. I/R (2.44 ± 0.13), P < 0.05). Further analysis showed that the variation in SENP3 expression was more obvious than that in Ubc9 under hypothermia intervention in the HT group. These findings suggest that selective cerebral hypothermia could increase SUMO2/3 modification mainly via down-regulating the expression of SENP3, and then exert neuroprotective effects in rats with cerebral I/R injury.

Thermal management with and without servo-controlled system in preterm infants immediately after birth: a multicentre, randomised controlled study.

BACKGROUND: The thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed. OBJECTIVE: To compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth. STUDY DESIGN AND SETTING: Multicentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals. PARTICIPANTS: Infants with estimated birth weight <1500 g and/or gestational age <30+6 weeks. INTERVENTION: Thermal management with or without a thermal servo-controlled system during stabilisation in the delivery room. PRIMARY OUTCOME: Proportion of normothermia at NICU admission (axillary temperature 36.5°C-37.5°C). RESULTS: At NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C-36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01). CONCLUSIONS: In very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge. TRIAL REGISTRATION NUMBER: NCT03844204.

Hypothermia induces opposite response in vascular and non-vascular smooth muscles.

BACKGROUND AND AIM: The mechanism of cooling-induced response of smooth muscles remains little understood despite the increasing importance given to it in recent years. The aim of this study was to examine the possibility of releasing a relaxant or a contractile substance during cooling from vascular and non-vascular smooth muscles. METHODS: Assessing the effect of cooling for two different smooth muscles together, vascular (aorta or carotid) which induced relaxation, and non-vascular (jejunum or bladder) which induced contraction. Hanging a pair of smooth muscle strips from different body organs in the same organ bath filled with Krebs solution, each strip was connected to its own transducer and recorder and stepwise cooling was applied. Recordings of isometric tension using organ-bath techniques. RESULTS: Step-wise cooling (37 °C-4 °C) of aorta and carotid smooth muscle preparations induced reproducible graded relaxation while jejunum and bladder preparations induced reproducible graded tonic contractions, inversely proportional to temperature. The responses of all the smooth muscle preparations were the same magnitude either alone or as a pair in the organ bath. Cooling abolished rhythmic smooth muscle activity of jejunum and bladder. Cooling-induced contraction was reduced by incubation in Ca2+-free solution. The effect of cooling either relaxation or contraction was not enhanced or attenuated by the presence of the two different smooth muscles with opposite response in the same organ bath, proving the absence of a relaxant or a contractile substance released during cooling. CONCLUSIONS: Cooling of aorta and carotid artery induced relaxation while jejunum and bladder induced contraction. The response to cooling is inversely proportional to the temperature. There was neither a relaxant nor a contractile substance released from vascular or non-vascular smooth muscles during cooling. Our study suggested that the effect of cooling is through a thermal receptor with two subtype one in the vascular smooth muscle (deep blood vessels) which induces relaxation, and the second in non-vascular smooth muscles (non-vascular organs) that induces contraction and the responses depend on extracellular calcium.

Effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in Sprague-Dawley and Wistar rats.

An inhalation system based on e-cigarette technology produces hypothermic and antinociceptive effects of Δ9-tetrahydrocannabinol (THC) in rats. Indirect comparison of some prior investigations suggested differential impact of inhaled THC between Wistar (WI) and Sprague-Dawley (SD) rats; thus, this study was conducted to directly compare the strains across inhaled and injected routes of administration. Groups (N = 8 per strain) of age-matched male SD and WI rats were prepared with radiotelemetry devices to measure temperature and then exposed to vapor from the propylene glycol (PG) vehicle or THC (25-200 mg/mL of PG) for 30 or 40 min. Additional studies evaluated effects of THC inhalation on plasma THC (50-200 mg/mL) and nociception (100-200 mg/mL) as well as the thermoregulatory effect of intraperitoneal injection of THC (5-30 mg/kg). Hypothermic effects of THC were more pronounced in SD rats, where plasma levels of THC were identical across strains, under either fixed inhalation conditions or injection of a mg/kg equivalent dose. Strain differences in hypothermia were largest after i.p. injection of THC, with SD rats exhibiting dose-dependent temperature reduction after 5 or 10 mg/kg, i.p. and the WI rats only exhibiting significant hypothermia after 20 mg/kg, i.p. The antinociceptive effects of inhaled THC (100, 200 mg/mL) did not differ significantly across the strains. These studies confirm an insensitivity of WI rats, compared with SD rats, to hypothermia induced by THC following inhalation conditions that produced identical plasma THC and antinociception. Thus, quantitative, albeit not qualitative, strain differences may be obtained when studying thermoregulatory effects of THC. (PsycInfo Database Record (c) 2021 APA, all rights reserved).