The effect of temperature on vascular smooth muscle: cooling-induced vasodilation in deep arteries and veins.

Blood vessels in the cardiovascular system include arteries and veins, which are responsible for moving blood to and from tissues around the body. Our previous studies showed that cooling induces relaxation of arteries. The aim of this study is to investigate the effect of cooling on both arteries and veins pairs. Isometric tension was recorded in rat artery ring preparations (aorta, carotid, pulmonary arteries) and their vein pairs (vena cava, jugular, pulmonary veins) in organ baths during stepwise cooling from 37 to 4 °C. Cooling responses were tested before and after the addition of various standard agents. The possibility of the presence of a cooling-relaxed substance and the influence of endothelium were also examined. Cooling-induced relaxation of both arteries and veins and the degree of relaxation were inversely proportional to the temperature. The cooling response was highest in arteries than their respective paired veins. The relaxation response was not endothelium dependent or affected with neurogenic mechanism (autonomic blockers or tetrodotoxin). Additionally, it was not changed by alterations of extra- or intra-cellular calcium transfer, and no relaxant substance was released from vascular smooth muscles during cooling. The study showed that cooling induces relaxation of both arteries and veins. Our results suggested that the effect of cooling could be through a thermal receptor in the vascular smooth muscle. Therefore, cold temperature can act as an agonist and increase in cooling temperature behaves as increase in concentration of the agonist. This study contributes to a better understanding of the mechanisms behind cooling-induced relaxation of blood vessels, which may have implications for the treatment of cardiovascular diseases.

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.

Effect of Verapamil on Kidney Function Using Radionuclide Imaging.

BACKGROUND AND OBJECTIVE: Calcium channel blockers (CCBs) are among the most widely used prescribed drugs for the treatment of cardiovascular diseases. The present study investigates the effect of verapamil, which is most commonly used as a CCB, on kidney function using radionuclide imaging. METHODS: Ten New Zealand white rabbits were used in vitro (4) and in vivo (6) studies. Isometric tensions were recorded for isolated renal artery ring segments, while renographic studies were performed using Technetium-99m mercaptoacetyltriglycine and Gamma camera. Time to peak activity (Tmax) and time from peak to 50% activity (T1/2), were calculated from the renograms for control and treated rabbits with verapamil. RESULTS: In vitro, verapamil shifted the curve of phenylephrine concentration-dependent contraction on renal artery to the right, and decrease the highest contraction by 30 ± 3%. In vivo, the average values of Tmax for control and treated rabbits were 2.8 ± 0.1 and 2.2 ± 0.2 min respectively. The T1/2 for control and treated rabbits were 4.7 ± 0.05 and 4.2 ± 0.08 min respectively. The differences were statistically significant: p < 0.05. There is 30 ± 4% decrease in the 2 values. This indicates that there is a rapid renal uptake of the tracer and clearance of the radioactivity after verapamil. CONCLUSION: Verapamil dilates the renal artery and accelerates both the Tmax and T1/2 in the renogram. It increases renal blood perfusion and protects kidney function and therefore improves its work. However, verapamil should not be used while performing renograms to avoid misleading results.

Effect of pregnancy on the cholinergic responses of the bladder: role of acetylcholinesterase.

OBJECTIVES: Pregnancy is associated with many functional changes of the urinary bladder. It was reported that most of healthy women complain from urinary symptoms during pregnancy. The parasympathetic system is mainly mediating bladder emptying. The aim of the study is to investigate the cholinergic effect and the role of acetylcholinesterase in the bladder during pregnancy. METHODS: Sixteen rats were used in the present study as control group (non-pregnant) and pregnant group (18-20 days pregnant). Isolated urinary smooth muscle strips were suspended in organ baths filled with Krebs' solution for isometric tension recording. RESULTS: Electric field stimulation (EFS), (0.1-40 Hz), of the control and pregnant bladder preparations produced frequency-dependent contractions. Atropine (1 µM) inhibited EFS-induced contractions in the two groups by 65% and 50% respectively indicating the response of cholinergic innervation. Neostigmine significantly enhanced EFS responses, confirming its selectivity for inhibiting acetylcholinesterase which is responsible for termination of acetylcholine. Concentration-response curves for acetylcholine were reduced in pregnant group than control. Concentration-response curves for ATP were increased in pregnant group than control. Neostigmine augmented concentration-response curves for acetylcholine in control and pregnant groups. The effect of neostigmine on acetylcholine contractile responses in pregnancy group was higher than in control. CONCLUSIONS: Urinary bladder dysfunction during pregnancy might be due to augmentation of acetylcholinesterase effect. This will lead to the decrease in response to cholinergic stimuli. New pharmaceutical drugs specifically affecting the enzyme in the bladder can help in avoiding the unpleasant urinary symptoms during pregnancy.

Heating-induced contraction in airways smooth muscle: A possible causative factor of exercise-induced bronchoconstriction.

Asthmatic patients often suffer from bronchoconstriction or asthma following breathing hot air or exposure to exercise due to raises the core body temperature. However, the direct effect of heating airways has not been studied yet. The aim of this study is to investigate the effect of heating on tracheal and bronchiolar smooth muscles. Isolated ovine tracheal strips and bronchiolar segments preparations were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissues responses were examined during decreasing and elevating baths temperature (20 °C, 40 °C-45 °C and 50 °C). Cooling or heating induced rapid and reproducible contractions proportional with decreasing or increasing temperature respectively in tracheal and bronchiolar preparations. On reset to 37 °C the tone returned rapidly to basal level. Changing the bath's temperature from 37 °C to 20 °C or to 40 °C and 45 °C for tracheal strips or to 45 °C and 50 °C for bronchiolar segments induced contractions in both preparations. Changing the temperature below or above the normal body temperature (37 °C), leads to airways contractions. Heating induced contractions in tracheal and bronchiolar smooth muscle proportional to the heating temperature. Therefore, breathing hot air or elevation of body core temperature due to exercise can be considered possible causative factor of heating- or exercise-induced bronchoconstriction.

Effect of pregnancy on cooling tone and rhythmic contractions of the rat urinary bladder.

OBJECTIVES: Pregnancy is a physiological alteration that can affect urinary bladder. Cooling of urinary bladder smooth muscle is known as a potent stimulus to micturition due to an increase in muscle tone. The current study investigates the effects of pregnancy on cooling tone and on the rhythmic contractions of the urinary bladder. METHODS: Twenty-four rats were used in this study as control group (non-pregnant) and pregnant group (18-20-day pregnancy). Isolated rat urinary muscle strips were suspended in organ baths containing Krebs' solution for isometric tension recording. RESULTS: Cooling from 37 to 5 °C induced a rapid and reproducible increase in basal tone, proportional to cooling temperature. Cooling also increased the rhythmic activity (amplitude and frequency) at 30 and 25 °C, then decreased at 20 °C, and abolished at 15-5 °C. These responses were more pronounced in pregnant group than in control group. Rhythmic contractions were abolished in calcium-free, EGTA (1 mM)-containing Krebs' solution and in the presence of nifedipine, while they were not affected by CPA or TTX in both groups. Our investigation showed that the influx of extracellular calcium is important in inducing the rhythmic contractions. CONCLUSIONS: Pregnancy increases cooling-induced contraction in pregnant rat urinary preparations and its rhythmic contractions including amplitude and frequency than non-pregnant rat. Rhythmic contractions are myogenic in nature and highly extracellular calcium dependent. They may play a crucial role in urinary bladder overactivity and incontinence during pregnancy.

Ethanol potentiates heat response in the carotid artery via TRPV1.

AIM: Ethanol is one of the most widely used recreational drugs in the world. At high concentrations, it can induce carotid artery vasoconstriction. Hyperthermia potentiates its effects resulting in carotid artery vasoconstriction at any concentration. The aim of this study is to investigate the interaction between ethanol and heating and to understand the underlying mechanisms leading to their synergistic effect. MATERIALS AND METHODS: Isometric tension of rabbit carotid artery ring segments suspended in organ baths filled with Krebs solution was recorded. Different concentrations of ethanol were examined at 37°C and during temperature elevation to39-43°C. Capsaicin and capsazepine were used to examine the mechanism of action of ethanol. KEY FINDINGS: Ethanol induced contraction at 37°C when the concentration reached 100mM. Contraction was observed at any concentration at higher temperatures. Ethanol potentiated heat-induced contraction. Capsaicin, the vanilloid receptor subtype1 (TRPV1) agonist, potentiated the vasoconstriction due to heating. While capsazepine, TRPV1 antagonist, abolished the effect of ethanol and its potentiation of heating-induced contraction, but it did not abolish the heating effect. SIGNIFICANCE: Ethanol's mechanism of action and its effect on heating induced-vasoconstriction of the carotid artery is being mediated by TRPV1. The combination of ethanol and hyperthermia can lead to a synergistic effect on carotid vasoconstriction. This effect may induce brain damage and heat stroke. Development of new drugs act as TRPV1 antagonist can be used to prevent these fatal effects.

Evaluation of different anti-asthmatic drugs on cooling-induced bronchoconstriction.

BACKGROUND: Inhalation of cold air is a well-recognized cause of bronchoconstriction in asthmatics. Sudden changes in weather temperature outdoors and indoors due to the extensive use of air conditioning in Kuwait is an important existing problem. OBJECTIVES: The aim of this study was to determine the most effective anti-asthmatic drugs for preventing or reversing cooling-induced contraction (CIC). METHODS: We recorded isometric tension from tracheal strips, and bronchiolar rings were prepared from male Merino sheep in organ baths during stepwise cooling. CIC was tested before and after addition of various standard agents. Disodium cromoglycate (DSG), methyl prednisolone, atropine, aminophylline, isoprenaline and adrenaline were examined in two cases. The first was before cooling and the second was after cooling induced the maximum bronchoconstriction. RESULTS: Cooling to 20°C induced a rapid and reproducible contraction in ovine tracheal and bronchial preparations. On readjustment to 37°C, the tone returned rapidly to basal level. DSG, methyl prednisolone and atropine did not prevent or reverse the CIC. Aminophylline prevented CIC by 70%. It inhibited the peak of cooling response by 70%. ß-agonists (isoprenaline and adrenaline) abolished the CIC, and they also rapidly and totally reversed the cooling effect when added at the peak of bronchoconstriction. CONCLUSIONS: These results proved that ß-agonists are the drugs of choice in preventing the bronchoconstriction before exposure to cold environment and also completely reversing the bronchoconstriction induced after cooling exposure.

Reactivity of diabetic urinary bladder to the cholinesterase inhibitor neostigmine.

OBJECTIVE: To examine the effects of neostigmine, an acetylcholinesterase inhibitor that has been used to treat impaired bladder emptying on diabetic rat urinary bladder smooth muscle. METHODS: Rat urinary detrusor muscle strips were suspended in organ baths containing Krebs' solution for isometric tension recording. Streptozotocin-diabetic (12 weeks) bladder tissue activity compared with control was assessed by using electrical field stimulation (EFS) in the presence and absence of the cholinesterase inhibitor, neostigmine. RESULTS: EFS-induced contractions; a major part of it is cholinergic in origin. Neostigmine significantly enhanced EFS-induced contractions in diabetic strips than control at all frequencies. Neostigmine caused concentration-dependent contractions of control and diabetic bladder tissues, which were completely abolished by atropine. Carbachol-induced bladder contraction was significantly reduced in diabetes. CONCLUSION: In diabetes mellitus, cholinesterase modulation (increase) may play a role in the development of inadequate bladder contraction, seen in later stage diabetic bladder dysfunction.

Self-medication among undergraduate medical students in Kuwait with reference to the role of the pharmacist.

OBJECTIVE: The practice of self-medication is growing world-wide. It is associated with problems that may lead to potentially life-threatening complications represent a priority to be investigated. The aim of this study was to estimate the prevalence of self-medication among undergraduate medical students and to evaluate the possible role of the pharmacist in self-medication in Kuwait. METHODS: A descriptive cross-sectional study was performed, using the questionnaire on a sample of 900 male and female students randomly selected from three health faculties in Kuwait. The prevalence of self-medication, as well as the contribution of pharmacist in self-medication was assessed. In addition, the role of the pharmacist as drug consultant for the students after getting the medication was evaluated. FINDINGS: The overall prevalence of self-medication was 97.8%. The age was significantly inversely proportional to self-medication. There was a significant difference between male and female students in self-medication practice. Headache was the highest health conditions that most frequently motivated self-medication with 90.1% prevalence, followed by 84.7% for dysmenorrhea and 60.3% for constipation. Contribution of the pharmacist as a part of self-medication care was low totally, with the highest rate for cough conditions 40.1%. However, the role of the pharmacist as a drug consultant was more noticeable after obtaining the drug, not before. Around 80.1% of the students request information from the pharmacist about doses, duration of treatments and side-effects. CONCLUSION: The prevalence of self-medication among undergraduate students in Kuwait is high and there were significant differences for age and gender. The contribution of the pharmacist was low in self-medication, while it was high after getting the drugs for obtaining drug related information. The practice of self-medication is alarming. Improved awareness about the role of pharmacist as a drug consultant for careful and cautious use of medicines available for self-medication would be strongly recommended.

Effect of sulfa drugs on kidney function and renal scintigraphy.

AIM: The sulfonamide group is widely used for bacterial diseases including kidney and urinary tract infections. The present study investigates the effect of a sulfa drug on kidney function and renography studies by using a radionuclide. METHODS: Renography studies were performed on New Zealand white rabbits. Each rabbit was injected with 48.1 MBq technetium-99m mercaptoacetyltriglycine ((99m) Tc-MAG-3). Dynamic images were acquired using a gamma camera. Radioactivity time curves were generated from the regions of interest, time to peak activity (Tmax ) and time from peak to 50% activity (T1/2 ). Each rabbit served as its own control. The sulfa drug was given to these rabbits for 7 days (i.v injection 130 mg/kg daily in two divided doses; i.e. the single dose is 65 mg/kg), then dynamic images were acquired. RESULTS: Treatment with sulfa shifted the experimental curves to the right of the control curves. This result showed that there was a delayed renal uptake of (99m) Tc-MAG-3 and its clearance. Calculated averages of Tmax were 2.2 ± 0.3 and 5.9 ± 0.5 min; while for T1/2 were 3.1 ± 0.3 and 8.4 ± 0.6 min for control and sulfa-treated rabbits, respectively (n = 20; P < 0.05). CONCLUSION: Our results indicate that sulfa drug induced pharmacokinetic changes because of delaying both the Tmax and T1/2 . Sulfa drug has an effect on the reabsorption from the renal tubules and the excretion process of (99m) Tc-MAG-3 which is excreted almost exclusively by the renal tubules. Therefore, sulfa drug causes a deterioration in kidney function and an alteration on radionuclide renography.

Effect of the NSAID diclofenac on 99mTc-MAG3 and 99mTc-DTPA renography.

UNLABELLED: Renal function and disease are commonly evaluated by radionuclide studies. The choice of radiopharmaceutical agent for various studies is crucial for proper interpretation. (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) is excreted almost exclusively by the renal tubules, whereas (99m)Tc-diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) is predominantly excreted by glomerular filtration. The present study compared the effect of the nonsteroidal antiinflammatory drug (NSAID) diclofenac, which is the most commonly used drug to relieve kidney pain, on the kinetic behavior of administered (99m)Tc-MAG3 and (99m)Tc-DTPA in experimental animals. METHODS: Two groups of 12 New Zealand White rabbits ((99m)Tc-MAG3 and (99m)Tc-DTPA) were used for the renography. Each rabbit served as its own control. The animals were given 60 mL of saline intravenously 30 min before each renographic study. A baseline study (control) was done by injecting 48 MBq (1.3 mCi) of (99m)Tc-MAG3, and renography was performed. Two days later, a single intravenous dose of diclofenac (2 mg/kg) (treated animals) was given, and after 20 min, (99m)Tc-MAG3 renography was performed. This procedure was repeated for the (99m)Tc-DTPA group after administration of 96 MBq (2.6 mCi) of the tracer. Dynamic images (as 2-s frames for the first minute and 30-s frames for the next 30 min on a 64 × 64 matrix) were acquired using a γ-camera equipped with a low-energy high-resolution collimator interfaced with a computer. Regions of interest were drawn over the whole kidneys. Time-activity curves were generated from the region of interest. Time to peak activity (T(max)), time from peak to 50% activity (T(1/2)), and the uptake slope of each kidney were calculated from the renograms for control and treated rabbits. RESULTS: Administration of diclofenac shifted the experimental renogram curves to the right, compared with the control curves, indicating that there was a delayed renal uptake of the 2 tracers and clearance of the radioactivity. The calculated average values of T(max) for control and treated rabbits using (99m)Tc-MAG3 were 1.8 ± 0.5 and 6.35 ± 0.4 min, respectively, whereas those of (99m)Tc-DTPA were 3.4 ± 0.4 and 18.2 ± 2 min, respectively. The T1/2 for control and treated rabbits for (99m)Tc-MAG3 were 3.2 ± 0.07 and 6.6 ± 0.07 min, respectively, whereas those for (99m)Tc-DTPA were 10.1 ± 1 and 35 ± 4 min, respectively. The differences were statistically significant (P < 0.05). CONCLUSION: This study showed that diclofenac delayed both T(max) and T1/2. The NSAID-induced kinetic changes were considerably greater for (99m)Tc-DTPA than for (99m)Tc-MAG3. On the basis of these findings, it is suggested that (99m)Tc-MAG3 be used to perform renography for studies involving the use of NSAID administration to decrease any change that may occur due to the type of tracer and not to the condition of the kidney.

Effect of diabetes on the ion pumps of the bladder.

OBJECTIVE: To establish whether the activities of Na+/K+-adenosine triphosphatase (ATPase) and Ca2+-ATPases ion pumps in bladder smooth muscle are altered as a consequence of diabetes and, if so, how this might contribute to bladder cystopathy. Urinary bladder dysfunction is a common occurrence in patients with diabetes. Pressure generation requires calcium and cytosolic ATP. Activities of these pumps are responsible for calcium homeostasis. METHODS: Rat urinary detrusor muscle strips were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to the Na+/K+-ATPase pump inhibitor, ouabain, the plasma membrane Ca2+ ATPase inhibitor, vanadate, and the sarcoplasmic reticulum Ca2+ ATPase inhibitor, cyclopiazonic acid (CPA), were examined from normal and streptozocin-induced diabetic rats for 2, 4, and 12 weeks. RESULTS: Ouabain, vanadate, and CPA caused concentration-dependent contractions of bladder strips from diabetic and normal rats. The degree of contraction of diabetic bladder muscle was lower than that of controls. This reduction was a function of duration of diabetes. For ouabain, the reduction peaked at 2 weeks, with partial restoration to normal after diabetes induction. For vanadate and CPA, the reduction increased with the duration of diabetes. CONCLUSION: The ion pumps are important modulators of bladder smooth muscle tone, and in a rat model of streptozotocin-induced diabetes, the activity of these pumps is impaired. Although this is only a single model of diabetes, these findings suggest that a defect in these pumps may be an important component of the development of diabetic bladder cystopathy.

Effect of ethnicity on erythropoietin therapy response for hemodialysis patients: a retrospective study.

Anemia is a common feature in chronic kidney disease patients due to deficiency of erythropoietin (EPO). Diseased kidneys are unable to produce EPO, which enhances red blood cell production from the bone marrow. Recombinant human EPO in hemodialysis patients was introduced with perfect outcomes as a hormonal substitutive treatment. Some ethnic minority groups have high prevalence of anemia associated with chronic kidney diseases. The aim of this study is to evaluate the differences between African Caribbeans and Caucasians' EPO therapy response with regard to hemoglobin (Hb), some factors affecting it and some comorbid conditions. A retrospective study for 6 months of 100 patients on hemodialysis was conducted on two ethnic minorities groups; 46 patients were African Caribbean and 54 patients were Caucasian, who received EPO therapy at once or three times weekly dose at the Hanbury Dialysis Unit of Royal London Hospital. There were three types of EPO therapy used: Aranesp, Mircera and Neorecormon. Forty-six patients were African Caribbean and 54 patients were Caucasian. There were 63.4% of patients treated by Aranesp while 13% were given Mircera; 22.8% of the sample used Neorecorman. It was shown that the chosen comorbid conditions had higher percentage in the African Caribbeans than in Caucasians. Diabetic and/or hypertensive patients are almost double the patient numbers. In addition, sickle cell anemia is only present in African Caribbeans. There were 43.5% of African Caribbeans and 81.1% of Caucasians who met the standards of Hb level. There was no significant difference between African Caribbeans and Caucasians regarding parathyroid hormone, c-reactive protein, B12, mean corpuscular volume, ferritin, and folate. In this study, there was a significant difference in the Hb levels between African Caribbean and Caucasian groups. Sixty percent of African Caribbeans had mean Hb less than normal levels. However, they received lower EPO dose than Caucasians. As a result, this may affect the whole treatment and therapy which may lead to anemic complications.

Detection of bacterial endotoxin in drinking tap and bottled water in Kuwait.

This study was carried out to measure and compare the concentration of bacterial endotoxin in a variety of samples from drinking tap and bottled water available in Kuwait by using the Limulus Amoebocyte lysate test. A total of 29 samples were tested. Samples were collected from a variety of locations throughout the six governorates of Kuwait and 23 brands of local and imported bottled water samples were collected from the local market. The concentration of bacterial endotoxin was measured by using the standard Limulus Amoebocyte lysate test, gel clot method. This study showed that measured endotoxin concentrations in tap drinking water varied from 2.4 to 33.8 EU/ml with the average endotoxin concentration of 14.2 EU/ml. While the results of endotoxin concentrations in the bottled water were <0.03 to 20.1 EU/ml with an average of 1.96 EU/ml. The average concentration of endotoxin in bottled water is 13.5 % of the average concentration of endotoxin in tap drinking water. This experimental investigation has proved that drinking bottled water has less endotoxin as compared to tap water in Kuwait. It is also demonstrated that the endotoxin concentration did not exceed the acceptable level in drinking tap water.

Effect of acute cold exposure on lung perfusion and tracheal smooth muscle contraction in rabbit.

Acute exposure to cold temperature can affect the respiratory system of those exposed to extreme weather and induces asthma in asthmatic patients. However, the effect on lung perfusion and the pulmonary circulation was not addressed in any previous study. The present study investigates the effects of acute cold exposure on tracheal smooth muscle and lung perfusion. New Zealand White rabbits were used in these experiments. For in vitro experiments, isolated tracheal segments were suspended in organ baths containing Krebs' solution for isometric tension recording. Tissue response to cooling from 37 to 4°C was examined. For in vivo experiments, the rabbits were kept in a cold room (4°C) for 1 h. Lung perfusion scintigraphy was performed at the end of this period. Each rabbit was injected with 74 MBq (2 mCi) technetium-99m macroaggregated ((99m)Tc MAA). Perfusion studies were done by using Gamma camera equipped with a low-energy, high-resolution, parallel-hole collimator interfaced with a computer. Static images were acquired 5 min after administration of the radiotracer. Cooling induced a rapid and reproducible contraction in the tracheal smooth muscle. Rabbits exposed to cold temperature had lesser lung perfusion than controls using radionuclide perfusion study. Our results highlight the response of tracheal muscle and pulmonary circulation to cold exposure. These results indicate that cooling induced contraction of the trachea and decreased pulmonary circulation and lung perfusion. This summation of acute cooling for tracheal smooth muscle and pulmonary circulation seems to be the reason for the severe cooling-induced contraction.

Effect of diabetes on cooling-induced detrusor muscle contraction: mediation via Rho-kinase activation.

OBJECTIVES: To investigate the possible involvement of Rho-kinase in cooling-induced contraction of the detrusor muscle. The etiology of diabetic cystopathy is not clear. It may be due to various changes in bladder innervation and/or detrusor muscle dysfunction. Because cooling of urinary bladder smooth muscle normally is a potent stimulus to micturition due to increase in muscle tone, we studied the effects of cooling on normal and diabetic bladder specimens. METHODS: Urinary detrusor muscle strips isolated from rats were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to stepwise cooling were examined from normal and 12-week streptozocin-induced diabetic rats. We examined the effects of calcium-free, ethylene glycol bis (beta-aminoethylether)-N,N,N,N,-tetraacetic acid (1 mm)-containing Krebs solution, and the Rho-kinase inhibitor Y-27632 on the cooling responses. RESULTS: Stepwise cooling from 37 degrees C to 5 degrees C induced a rapid and reproducible increase in basal tone, proportional to cooling temperature. This response was more pronounced in diabetic specimens. Cooling-induced contractions were significantly inhibited in calcium-free solutions in both control and diabetic bladders. Our investigation showed that the influx of extracellular calcium is important in inducing the cooling response. The Rho-kinase inhibitor Y-27632 (1 microm) inhibited cooling (20 degrees C)-induced contraction. It reduced the response by 52.1% +/- 10.0% in control and by 70.0% +/- 12.0% in diabetic rats. CONCLUSIONS: Cooling-induced contractions in control and diabetic detrusor muscle preparations are highly calcium dependant. It also involves activation of Rho-kinase, which might be upregulated in the diabetic detrusor muscle. These results may help in the management of diabetes-induced incontinence due to involuntary detrusor muscle activity.

Verapamil induces calcium influx in the trachea.

Verapamil, a Ca(2+) entry blocker, can induce bronchorelaxation and bronchoconstriction. The mechanism of verapamil-induced bronchoconstriction is poorly understood. The present study determines the direct effect of verapamil on smooth muscle of isolated ovine airways and analyzes the mechanisms involved. Isolated tracheal strips were suspended in organ baths containing Krebs solution for isometric tension recording. Tissue responses to verapamil as assessed by basal tone were examined in the presence or absence of epithelium. The effects of verapamil on carbachol and cooling-induced contraction were also recorded. Measurement of unidirectional fluxes was carried out using (45)Ca(2+) in the absence or presence of verapamil. Verapamil induced contractions of basal tracheal smooth muscle that were proportional to its concentrations. Removal of epithelium did not affect the verapamil contractile effect. Verapamil-induced contractions were abolished in Ca(2+)-free Krebs solution containing 2 mM EGTA. Verapamil increased the (45)Ca(2+) influx into the tracheal smooth muscle. It caused relaxation of the muscle tone induced by carbachol or KCl, but it potentiated the effect of cooling-induced contraction. Verapamil induced Ca(2+) influx that may lead to bronchoconstriction. These results proved that verapamil may worsen bronchoconstriction; therefore verapamil should be used with caution in asthmatic individuals.

Influence of hyperthermia on carotid blood flow using 99mTc-HMPAO.

Hyperthermia can be the result of many causes such as environmental conditions, brain tumors and infectious diseases. Since hyperthermia is very common, its role in causing stroke through a decrease in cerebral blood flow needed further emphasis. The aim of this study was to record cerebral blood flow in vitro by using isolated rabbit carotid artery strips and in-vivo using radioactive isotope scanning during temperature elevation. The recording of isometric tension in rabbit carotid artery strips in organ baths, and the scintigraphic cerebral imaging of technetium-99m-hexamethyl-propyleneamineoxime (99mTc-HMPAO) using Gamma camera, were acquired at control and higher body temperature by 4 degrees C. Blood pressure was measured through femoral artery and cerebral blood flow was measured through carotid artery. Elevating temperature by 4 degrees C induced reproducible contraction. During hyperthermia, the carotid artery contraction leads to a decrease in cerebral blood flow although the blood pressure did not decrease. The uptake of 99mTc-HMPAO in the brain was significantly reduced. This decrease in cerebral perfusion is regionally dependent, which is more in the frontal area, the cerebral hemispheres than the cerebellum. The decrease was 36+/-3, 37+/-2, 22+/-2%, respectively. Hyperthermia causes carotid artery contraction leading to decrease in cerebral blood flow, which was confirmed by 99mTc-HMPAO images. The decrease is regionally dependent. Since the blood pressure did not decrease by heating, the reduction in cerebral perfusion is mainly due to carotid contraction. The applied neck cooling may be considered as a promising therapeutic strategy for the hyperthermic patient to avoid brain damage. This can be achieved by external application of an ice-water-perfused neck collar.

Hyperthermia alters kidney function and renal scintigraphy.

BACKGROUND/AIM: Fever can be caused by different reasons such as environmental conditions, acute rejection after kidney transplantation and bacterial diseases including kidney and urinary tract infections. The present study represents a novel idea of investigating the direct effect of body temperature elevation on kidney function to determine whether hyperthermia alters the kidney function transiently leading to inaccurate findings and possible misinterpretation of the radionuclide (99mTc-MAG-3) renography studies. METHODS: Renography studies were performed on New Zealand White rabbits weighing approximately 3-3.5 kg. Each rabbit was inject with 48.1 MBq (1.3 mCi) technetium-99m-mercaptoacetyltriglycine (99mTc-MAG-3). Studies were acquired using a gamma camera equipped with a low-energy, high-resolution collimator interfaced with a computer. Dynamic images were acquired as 2-s frames for the first 1 min and every 30 s for the next 30 min on a matrix of 64 x 64. Regions of interest were drawn over the whole kidneys. Radioactivity time curves were generated from the regions of interest. Time to peak activity (Tmax), time from peak to 50% activity (T1/2), and the uptake slope of each kidney were calculated from the renograms. Three days later the same protocol was repeated for the same rabbit but with a higher body temperature by 2 degrees C. Then it was repeated with a higher body temperature by 3 degrees C, then 4 degrees C with the same interval period. Blood pressure was measured using a catheter inserted into the femoral artery connected to a Lectromid recorder at normal temperature and during increasing the temperature by 2, 3 and 4 degrees C. Renal blood flow was also measured via the renal artery using an electromagnetic blood flow sensor connected to a flowmeter. Creatinine and blood urea nitrogen (BUN) in blood were measured in control and hyperthermic rabbits. RESULTS: During hyperthermia the experimental curves shifted to the right of the control curves indicating that there was a delayed renal uptake of 99mTc-MAG-3 and clearance of radioactivity. This delay was proportional to body temperature. Calculated averages were: Tmax 1.6 +/- 0.1, 2.8 +/- 0.3, 8.8 +/- 1, 15 +/- 4 min; T1/2 2.77 +/- 0.2, 3 +/- 0.4, 8.9 +/- 1.1, 20 +/- 3.4 min, and perfusion index 190 +/- 5, 201 +/- 4, 218 +/- 7, 224 +/- 9 of control and hyperthermic (elevation of temperature 2, 3, and 4 degrees C) rabbits, respectively (n = 6; p < 0.05). Mean arterial pressure and renal blood flow did not significantly change during hyperthermia. Creatinine and BUN were proportionally elevated to high temperature. CONCLUSIONS: Our results indicate that hyperthermia causes a transient alteration in the function of the kidney and scintigraphic pattern on radionuclide renography. Radionuclide renography studies may be performed at normothermic temperature since interpretation at higher body temperature could lead to misleading results, and temperature should be checked and recorded for single and follow-up radionuclide renography studies.