Fuel reduction burning reduces wildfire severity during extreme fire events in south-eastern Australia.

Extreme fire events have increased across south-eastern Australia owing to warmer and drier conditions driven by anthropogenic climate change. Fuel reduction burning is widely applied to reduce the occurrence and severity of wildfires; however, targeted assessment of the effectiveness of this practice is limited, especially under extreme climatic conditions. Our study utilises fire severity atlases for fuel reduction burns and wildfires to examine: (i) patterns in the extent of fuel treatment within planned burns (i.e., burn coverage) across different fire management zones, and; (ii) the effect of fuel reduction burning on the severity of wildfires under extreme climatic conditions. We assessed the effect of fuel reduction burning on wildfire severity across temporal and spatial scales (i.e., point and local landscape), while accounting for burn coverage and fire weather. Fuel reduction burn coverage was substantially lower (∼20-30%) than desired targets in fuel management zones focused on asset protection, but within the desired range in zones that focus on ecological objectives. At the point scale, wildfire severity was moderated in treated areas for at least 2-3 years after fuel treatment in shrubland and 3-5 years in forests, relative to areas that did not receive fuel reduction treatments (i.e., unburnt patches). Fuel availability strongly limited fire occurrence and severity within the first 18 months of fuel reduction burning, irrespective of fire weather. Fire weather was the dominant driver of high severity canopy defoliating fire by ∼3-5 years after fuel treatment. At the local landscape scale (i.e., 250 ha), the extent of high canopy scorch decreased marginally as the extent of recently (<5 years) treated fuels increased, though there was a high level of uncertainty around the effect of recent fuel treatment. Our findings demonstrate that during extreme fire events, very recent (i.e., <3 years) fuel reduction burning can aid wildfire suppression locally (i.e., near assets) but will have a highly variable effect on the extent and severity of wildfires at larger scales. The patchy coverage of fuel reduction burns in the wildland-urban interface indicates that considerable residual fuel hazard will often be present within the bounds of fuel reduction burns.

New method of cardiac output measurement using ultrasound velocity dilution in rats.

The aim of this study was to validate a new technique for the measurement of cardiac output (CO) based on ultrasound and dilution (COUD) in anesthetized rats. A transit time ultrasound (TTU) probe was placed around the rat carotid artery, and ultrasound velocity dilution curves were generated on intravenous injections of saline. CO by COUD were calculated from the dilution curves for normal and portal hypertensive rats in which CO was known to be increased. COUD was compared with the radiolabeled microsphere method and with direct aortic TTU flowmetry for baseline CO and drug-induced CO variations. CO in direct aortic TTU flowmetry was the ascending aorta blood flow measured directly by TTU probe (normal use of TTU flowmetry). The reproducibility of COUD within the same animal was also determined under baseline conditions. COUD detected the known CO increase in portal hypertensive rats compared with normal rats. CO values by COUD were correlated with those provided by microsphere technique or direct aortic TTU flowmetry (adjusted r = 0.76, P < 10(-4) and r = 0.79, P < 0.05, respectively). Baseline CO values and terlipressin-induced CO variations were detected by COUD and the other techniques. Intra- and interobserver agreements for COUD were excellent (intraclass r = 0.99 and 0.98, respectively). COUD was reproducible at least 10 times in 20 min. COUD is an accurate and reproducible method providing low-cost, repetitive CO measurements without open-chest surgery. It can be used in rats as an alternative to the microsphere method and to direct aortic flowmetry.

Developmental changes in the pattern of amino acid transport at the blood-brain barrier in rats.

Oldendorf's method has been widely used to estimate and characterize the transport of amino acids across the blood-brain barrier in rats. However, it cannot be used with very young animals. A modification of this method (retrograde injection into the right brachial artery, instead of orthograde injection into the common carotid artery) allowed the estimation of the brain uptake index of some amino acids in 5-, 12- and 19-day-old rats, as well as the study of self- and cross-inhibition and of sodium dependency. The results obtained showed that the pattern of transport of amino acids was different in 5-day-old and in 19-day-old rats. In young rats, besides the presence of the L-system, which transported large neutral amino acids as in adult rats, the presence of another system of transport for neutral amino acids was strongly suggested. The activity of this system which transported alanine, serine, cysteine and threonine, decreased during development and it had many of the characteristics of the ASC system described by Christensen. In addition, the presence of a system of transport for beta-amino acids at the blood-brain barrier is suggested.

Measurement of collateral circulation blood flow in anesthetized portal hypertensive rats.

AIMS: The aim of this study was to develop a technique to measure collateral blood flow in portal hypertensive rats. METHODS: Morphological techniques included inspection, casts and angiographies of portosystemic shunts. The main hemodynamic measurements were splenorenal shunt blood flow (transit time ultrasound method), percentage of portosystemic shunts and regional blood flows (microsphere method). In study 1, a model of esophageal varices was developed by ligating the splenorenal shunt. In study 2, morphological studies of the splenorenal shunt were performed in rats with portal vein ligation. In study 3, the relationship between splenorenal shunt blood flow with percentage of portosystemic shunts was evaluated in dimethylnitrosamine cirrhosis. In study 4, secondary biliary, CCl4 and dimethylnitrosamine cirrhosis were compared. In study 5, rats with portal vein ligation received acute administration of octreotide. In study 6, rats with dimethylnitrosamine cirrhosis received acute administration of vapreotide. RESULTS: Blood flow of para-esophageal varices could not be measured. SRS blood flow was correlated with the mesenteric percentage of portosystemic shunts (r = 0.74, P < 0.05), splenic percentage of portosystemic shunts (r = 0.54, P < 0.05) and estimated portosystemic blood flow (r = 0.91, P < 0.01). Splenorenal shunt blood flow was 6 to 12 times higher in portal hypertensive rats, e.g., in portal vein ligated rats: 2.8 +/- 2.7 vs 0.3 +/- 0.1 mL.min-1 in sham rats (P < 0.01), and was similar in the different cirrhosis models but was higher in portal vein ligated rats than in cirrhotic rats (1.2 +/- 0.7 vs 0.6 +/- 0.6 mL.min-1.100 g-1, P = 0.05). Octreotide significantly decreased splenorenal shunt blood flow: -23 +/- 20% (P < 0.01) vs -6 +/- 8% (not significant) in placebo rats. The variation of splenorenal shunt blood flow after vapreotide was significant but not that of the splenic percentage of portosystemic shunts compared to placebo. CONCLUSIONS: The splenorenal shunt is the main portosystemic shunt in rats. The measurement of splenorenal shunt blood flow is easy, accurate and reproducible and should replace the traditional measurement of the percentage of portosystemic shunts in pharmacological studies.

[Analgesic effect of tiapride in healthy volunteers]. / Les effets antalgiques du tiapride chez le volontaire sain.

Twenty male volunteers, average age 23, were studied in the fasting state at a week interval in the morning between nine and ten a.m. A brachial blood pressure cuff was inflated to a pressure of 250 mmHg and the subject squeezed a hand dynamometer to half of maximum strength for two ten seconds periods. The subject then started to report his sensory experience every ten seconds for 15 minutes by pointing at a scale consisting of six categories from "nothing" to "extremely painful". The first trial was performed on all unmedicated subjects, the non dominating arm was used. The second trial was performed on the opposite arm, 45 minutes after oral double-blind randomized administration of a capsule containing either 1 g aspirin or 300 mg tiapride. The answers of the subjects were statistically analysed using paired comparisons tests. Results indicate that tiapride exerts a significant antalgic effect from the 6th minute to the end of the experiment when compared to the control (p less than 0.05 to p less than 0.01). Aspirin produces a similar antalgic effect which occurs earlier, after 4 minutes. The mechanism of the antalgic effect of tiapride has been attributed to the release of beta-endorphine produced by benzamide which is associated with a decrease in plasma dopamine and a parallel increase in prolactine.

[Calcium channel modulators as antidotes in fatal imipramine poisoning]. / Effets antidotes de certains modulateurs des canaux calciques dans l'intoxication létale à l'imipramine.

Calcium entry modulators were tested as antidotes to imipramine lethal toxicity. 42 rats were administered intraperitoneally 85 mg/kg of imipramine. In 6 control rats, hypotension and bradycardia were observed. Survival time was 15' +/- 5'. Survival time of rats treated with intraarterial nitrendipine was 21' +/- 11'. Survival time of 5 out of 6 rats treated by intraarterial verapamil or diltiazem was respectively 19'00" +/- 14'30" and 40'30" +/- 32'00". 5 out of 6 rats treated by intraarterial nimodipine, as well as all of the rats treated by flunarizine or nicardipine survived and were alive and active 48 hours later. Intoxication with imipramine may induce life threatening complications for which there are no specific medication. Nicardipine might be considered in the treatment of acute poisoning by imipramine and related tricyclic compounds.

[Cocaine and disturbances of adrenergic neurotransmission]. / Cocaïne et perturbation de la neurotransmission adrénergique.

Cocaine releases peripheral and central stores of catecholamines and their plasma concentration increases in very significantly under the influence of the drug. One also observes a vaso-constriction of cerebral and coronary arteries. Decreases in blood flow through those vessels have been observed in cocaine addicts examined with the magnetic resonance and positron emission tomography techniques. Some of these changes may still be present 15 days after withdrawal. The authors suggest an hypothesis to account for the general mode of action of cocaine. The synaptic increase in catechol produced by this drug is calcium dependent and would induce an "up regulation" of receptor proteins of calcium channels with increased calcium intracellular fluxes. There would be an increase in catecholamine neuronal turnover and synthesis not a depletion. Conversely the adrenergic post-synaptic receptors would undergo a "down regulation". Such impairment of adrenergic neurotransmission is associated with an increase in Angiotensin II release and a decreased GABA activity. Sensory stimuli resulting from this impairment induce a dominant memory associated with drug seeking and consuming behavior.

[Potentiation of the acute toxic effects of cocaine by ethyl alcohol]. / Potentialisation des effets toxiques aigus de la cocaïne par l'alcool éthylique.

Ethyl alcohol increases significantly the lethality of cocaine intoxication in the rat. This lethality is not modified by nicardipine or flunarizine, antidotes to cocaine, and might be due to the formation of a newly identified active metabolite cocaethylene. In addition alcohol like cocaine inhibits the baro receptor reflex.

Cardiac dynamics of the Langendorff perfused heart.

The Langendorff perfused heart is studied in a closed system with (i) automatic regulations to maintain constancy of the perfusion column (Krebs-Henseleit + 0.5% albumin or 25-30% washed erythrocyte suspension), (ii) continuous recording of rate, coronary flow, and supravalvular aortic pressure. A microcomputer with software interface is used for storage treatment and on-line analysis of the recorded variables. In 38 preparations perfused with Krebs-Henseleit, minimal diastolic (61.2 +/- 2.8 mm Hg) is significantly below and peak systolic (98.7 +/- 3.6 mm Hg) significantly above perfusion pressure (80 mm Hg). Pressure difference between minimal diastolic and peak systolic (delta P) is 37.5 +/- 1.8 mm Hg. Increases in perfusion pressure will be associated with increases of coronary flow and delta P, which is also increased by isoprenaline administration. Oxygen consumption decreased by 76% when perfusion pressure was lowered from 80 to 60 mm Hg in hearts perfused with a 30% erythrocyte suspension. All of these experimental results were interpreted as indicating that delta P measured in this system resulted from an ejected volume (x acceleration) from the heart. The ejected volume corresponds to a valvular leak caused by the rigid nature of the system which is devoid of aortic compliance. delta P may be considered an index of left ventricular performance, an indication that the Langendorff preparation studied under the present conditions is a working heart. A 100-microliter volume constant infusion syringe for time administration of cardioactive drugs may be inserted at the base of the perfusion column to obtain dose-response effects.

Effects and interactions of natural cannabinoids on the isolated heart.

A Langendorff perfused rat heart preparation was designed to process dose-response effects of cardioactive drugs on rate, coronary flow, and supraaortic differential pressure (delta P; an index of cardiac performance). In this preparation, delta 9- -tetrahydrocannabinol (THC) 2 X 10(-6) M to 10(-5) M induces in the isolated perfused rat heart a biphasic increase in rate (maximal at 8 X 10(-6) M). Tachycardia is associated with decreases in (delta P) and no change or decreased coronary flow. Cardiac toxicity is observed with 3 X 10(-5) M. Cannabidiol (CBD) at concentrations of 9 X 10(-6) M to 10(-4) M has limited effect on rate while increasing delta P and coronary flow. Cannabinol (CBN) 8 X 10(-6) M to 3 X 10(-4) M depresses rate and delta P while coronary flow remains constant. Simultaneous equimolar administration of THC with CBD antagonizes or mitigates the cardiac effects of THC on rate, delta P, and coronary flow.

[A technic for selection of antidotes to an acute lethal poisoning]. / Une technique pour la sélection d'antidotes à une intoxication létale aiguë.

The dose of a toxic substance which is lethal to the rat within 15 min (LD100.15 min) and its specific antidotes are defined. Atropine, diazepam and nimodipine in sequential administration are effective antidotes to a LD100.15 min (1.5 mg/kg) of paraoxon, an anticholinesterase.

Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine.

Nitrendipine, a Ca2+ modulator was tested in the rat as an antagonist to the cardiac toxicity of cocaine and as an antidote to the acute lethal effects of this drug. In a first series of experiments, nitrendipine (1.46 X 10(-3) mg/kg/min) when simultaneously administered intraarterially with cocaine (2 mg/kg/min) suppresses the arrhythmias induced by cocaine and increases survival time from 73 +/- 33 min to 309 +/- 118 min and the lethal dose of cocaine from 146 +/- 66 mg/kg to 618 +/- 236 mg/kg (p less than 0.003). Nitrendipine also protects the heart from the acute morphological lesions induced by cocaine administration and antagonizes some of the central effects of cocaine. In a second series, 5 rats administered 60 mg/kg of cocaine intraperitoneally had a survival time of 8'06 +/- 5'20. Death was attributed to convulsions and respiratory arrest. Animals treated with nitrendipine (129 +/- 23 mg/kg) 4'30" after cocaine administration survived. Nitrendipine appears to have general protective effects against cocaine cardiac toxicity and the acute lethal effects of this alkaloid.

Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity.

Flunarizine and nimodipine, Ca2+ modulators which exert antagonist effects against catecholamines and serotonin and have specific action on the brain, were used as antidotes to imipramine toxicity in the rat. Imipramine, a tricyclic antidepressant, inhibits synaptic reuptake of catecholamines and serotonin. Flunarizine administered concurrently with imipramine increased survival time significantly (p less than 0.04). After a lethal dose of imipramine (85 mg/kg) 5 out of 5 animals treated with flunarizine (2.37 +/- 1.21 mg/kg in divided doses) and 4 out of 5 animals treated with nimodipine (0.36 +/- 0.11 mg/kg) survived. The acute toxicity of imipramine might be related, in part, to drug-induced alteration in turnover of excitatory neurotransmitters which will induce intracellular Ca2+ accumulation and damage to vital organs. These toxic effects of endogenously produced neuroamines may be antagonized by nimodipine or flunarizine.

Microvascular effects of cocaine; interaction with nitrendipine and enalaprilat.

Cocaine abuse can cause cardiovascular damage leading to hypertension, myocardial ischaemia and infarction. This might be partly due to the effects of cocaine on the microcirculation about which little is known, although its effects on the macrovessels are well documented. Accordingly, we used in vivo videomicroscopy to study the vasoconstrictive effect of cocaine on arterioles of different diameter. They were classified into three orders (A2, A3, A4) according to their position in the microvascular network and their diameter. Since calcium antagonists have been reported to exert a protective effect against the cardiovascular disorders induced by cocaine, we tested the hypothesis that this protective action occurs in the microcirculation. We found that intra-arterial administration of the calcium antagonist Nitrendipine greatly inhibited the vasoconstriction induced by cocaine in all three arteriole orders. The degree of inhibition ranged from 44 to 56%. Combined administration of benzodiazepine and an angiotensin converting enzyme inhibitor has also been reported to protect rats against cocaine-induced hypertension and to increase survival rates after a toxic dose of cocaine. Since the mechanisms of this protection are not yet clear, we also studied the effect of the angiotensin converting enzyme inhibitor Enalaprilat on cocaine-induced vasoconstriction. Intra-arterial administration of Enalaprilat inhibited this vasoconstriction slightly but significantly in arteriole orders 2 and 3 by 27 and 24% respectively, but not in order 4. We concluded that Nitrendipine is a powerful inhibitor of cocaine-induced vasoconstriction in the microcirculation. The small but significant inhibition found with Enalaprilat for the larger arterioles suggests that the local angiotensin II level may affect the response to cocaine. However, since the Enalaprilat-induced inhibition was very limited, we conclude that mechanisms other than those occurring in the peripheral microcirculation account for the protection afforded by Enalaprilat against the harmful effects of cocaine.

Antidotes to lethal cocaine toxicity in the rat.

Cocaine, like catecholamines or angiotensin II, may induce lethal cardiac or cerebral damage. Restrained rats were fitted with a caudal arterial catheter for on-line cardiovascular monitoring and antidote administration. They were given 60 mg/kg of cocaine i.p., a dose which produces behavioral and cardiovascular effects, convulsions and death in an average time of 10 min. Selected antidotes were administered 5 min after the lethal dose of cocaine. Incidence of lethality was not changed by propranolol, prazosin, labetalol, diazepam or enalaprilat, a converting enzyme inhibitor. Animals treated with any one of the following agents, alpha- or beta-blockers, diazepam or competitive inhibitors of angiotensin II [Sar-1-ile-8] and [Sar-1-thr-8] angiotensin II, presented myocardial infarction. All animals treated with calcium channel antagonists or enalaprilat, whether they survived or not, did not present myocardial infarction. Treatment with nitrendipine, flunarizine or diltiazem, resulted in survival of the animals with no observable aftereffects. Similar results were observed when enalaprilat was administered, with diazepam as an antidote, to a lethal dose of cocaine. Antagonists to the sympatho-adrenal system and to the renin angiotensin system appear to be effective antidotes to cocaine toxicity in the present experimental model.