National climate policies across Europe and their impacts on cities strategies.

Globally, efforts are underway to reduce anthropogenic greenhouse gas emissions and to adapt to climate change impacts at the local level. However, there is a poor understanding of the relationship between city strategies on climate change mitigation and adaptation and the relevant policies at national and European level. This paper describes a comparative study and evaluation of cross-national policy. It reports the findings of studying the climate change strategies or plans from 200 European cities from Austria, Belgium, Estonia, Finland, France, Germany, Ireland, Italy, Netherlands, Spain and the United Kingdom. The study highlights the shared responsibility of global, European, national, regional and city policies. An interpretation and illustration of the influences from international and national networks and policy makers in stimulating the development of local strategies and actions is proposed. It was found that there is no archetypical way of planning for climate change, and multiple interests and motivations are inevitable. Our research warrants the need for a multi-scale approach to climate policy in the future, mainly ensuring sufficient capacity and resource to enable local authorities to plan and respond to their specific climate change agenda for maximising the management potentials for translating environmental challenges into opportunities.

Effects of dexmedetomidine on systemic and coronary hemodynamics in the anesthetized dog.

In addition to central effects, which are the basis of their use in anesthesiology, alpha 2-adrenergic agonists have direct peripheral cardiovascular effects. Dexmedetomidine (DM) has been found to depress cardiac function in dogs, even after autonomic denervation. The present experiments evaluated the effects of DM on coronary flow, myocardial oxygen extraction, and cardiac function in intact, open chest dogs under enflurane anesthesia. Heart rate (HR), mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP), the first derivative of systolic left ventricular pressure (dP/dtmax), and flow in the left anterior descending coronary artery (CBF) were measured and continuously recorded. Cardiac output (CO), plasma catecholamines (CA), hemoglobin and oxygen saturation in arterial, mixed venous, and coronary sinus blood were measured at intervals. Cardiac index (CI), systemic vascular resistance index (SVRI), regional coronary vascular resistance (CVR), and oxygen concentration differences across the systemic [C(a-v)O2], and coronary [C(a-cs)O2] circulations were calculated. DM doses of 0.25, 0.5, 1.0, 2.0, and 4.0 micrograms/kg were given IV at 20-minute intervals. Measurements and samples were taken at peak drug effects and just prior to the next dose. The alpha 2-antagonist atipamezole, 0.5 mg/kg, was given after the last dose of DM. DM caused immediate dose-dependent increases in SVRI, CVR, LVEDP, C(a-v)O2, and C(a-cs)O2, and decreases in HR, and CI, with recovery between doses. DP/dtmax declined after the first two doses and stabilized thereafter, as plasma CA fell to minimal levels. Atipamezole completely reversed all changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dexmedetomidine, an alpha 2-adrenergic agonist, in the isolated heart.

Dexmedetomidine (DM) was studied in the isolated dog heart in the form of a Starling heart-lung preparation, (HLP). Hearts were subjected to increased loading by (a) increasing cardiac output, and (b) increasing systemic resistance. Results are depicted by cardiac function curves, prepared by plotting left atrial pressure against either systemic cardiac output or mean arterial pressure. DM, given in divided doses up to 44 micrograms, had no effect on heart rate or cardiac function, nor did injection of 0.5 mg of atipamezole, a selective alpha 2-antagonist. Additional injections of very large doses of DM, up to 4,444 micrograms, caused an increase in heart rate and a leftward shift of the function curves, ie, positive chronotropic and inotropic effects. Plasma catecholamine levels increased markedly between the 444 micrograms and the 4,444 micrograms cumulative doses of DM. Administration of 1 mg of prazosin had no effect, but 1 mg of propranolol returned the rate to baseline and markedly shifted function curves to the right and depressed their slopes. Thus, whereas low doses (corresponding to between 1 and 30 micrograms/kg in intact animals) of DM, given acutely IV, have been shown to depress cardiac function in intact and denervated dogs, this effect is not due to a direct effect on the myocardium. High doses, far beyond doses maximally effective in intact animals and man, release catecholamines from cardiac stores. Plasma DM levels after low doses in the HLP were between 1 to 10 times those seen in intact animals and human volunteers after the usual doses given clinically for their central effects. Because DM caused no myocardial depressant effect in the isolated, blood-perfused canine HLP, decreases in cardiac function seen after this drug is given to intact and autonomically denervated dogs must be due to factor(s) other than a direct action on the myocardium.

Alpha 2-adrenergic agonists in cardiovascular anesthesia.

At this time, the unique attributes of alpha 2-agonists in anesthesia lie in their ability to blunt the adrenergic response to the stresses of major surgery, in patients in whom this response is especially undesirable, without incurring the penalty of respiratory depression that attends the use of opioids. It has become more and more apparent that sympathetic/adrenergic activation often has adverse consequences for patient morbidity and mortality, and modification of such activation by drugs may be a valuable option for the anesthesiologist. However, at present, the evidence supporting this statement is "soft," such as improved hemodynamic and metabolic stability. What must be done is to generate solid support in the form of well-designed outcome studies. The potential value of alpha 2-agonists is greatest in major surgery in brittle patients involving the risk of significant adverse outcome. There are plenty of adequate anesthesia regimens to cover lesser surgical interventions. In these cases, it is not the choice of a specific anesthetic agent or technique, but rather the competence and diligence of the anesthesiologist that is most important for outcome. In contrast, in major cardiovascular surgery in high-risk patients, the optimal anesthetic approach attains more importance, and is still undecided. The final consensus as to whether or not this optimal approach will include the use of alpha 2-adrenergic agonists will depend on the results of more extensive clinical investigations.

Hemodynamic effects of dexmedetomidine, an alpha 2-adrenergic agonist, in autonomically denervated dogs.

The hemodynamic effects of the alpha 2-adrenergic agonist, dexmedetomidine (DM), were studied in eight anesthetized, autonomically denervated dogs. Autonomic block decreased mean arterial pressure (MAP) and cardiac index (CI) by approximately 20% to 95 +/- 8 mm Hg and 4.1 +/- 0.1 L/min/m2, respectively (mean +/- SEM), and reduced norepinephrine (NE) and epinephrine plasma levels to almost undetectable levels. DM, administered intravenously (i.v.) either by bolus injection or by slow (20 min) infusion in doses between 1 and 30 micrograms/kg, had no effect on heart rate (HR), increased MAP significantly by 98%, decreased CI by 59%, and increased calculated systemic vascular resistance index (SVRI) significantly by 376%, maximally. The effect of the lowest dose was mediated mainly by arteriolar vasoconstriction, and that of higher doses was mediated by vasoconstriction and decreased CI. Left ventricular end-diastolic pressure (LVEDP) increased significantly from 6 +/- 2 to greater than 30 mm Hg. maximally. The effects were cumulative, and the first dose caused near maximal pressor effect; the resistance increase was as great with slow infusion as with bolus injection. Prazosin (1 mg/kg) did not affect the changes, but 0.3 mg/kg atipamezole, a selective alpha 2-antagonist, completely antagonized them. These observations demonstrate potent constriction of both arteriolar resistance and venous capacitance vasculature in dogs. The combination of decreased CI and increased filling pressure implies marked decrease in cardiac function which was, however, fully reversible by atipamezole.

Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine.

Reversal of opioid effects by naloxone (NX) can lead to significant cardiovascular problems. We have reported previously that hypercapnic dogs develop greater increases in blood pressure and plasma catecholamine (CA) levels than hypocapnic ones when reversed with naloxone. We have also demonstrated differences between NX and nalbuphine (NBPH) in producing excitatory adrenergic responses when administered during normocapnia. The present study was designed to investigate possible dissimilarities in cardiovascular and sympathetic events after administration of either NX or NBPH in dogs made hypercapnic following fentanyl administration. After induction of anaesthesia with thiopentone and intubation, two groups of dogs were maintained with controlled ventilation on enflurane in oxygen anaesthesia and given 50 micrograms.kg-1 fentanyl IV. This caused a significant decrease in heart rate (HR) (P less than 0.001), mean arterial blood pressure (MAP) (P less than 0.001), and plasma concentrations of norepinephrine (NE) (P less than 0.002). Then, ventilation was decreased to produce a PaCO2 of 60 mmHg; this was accompanied by a significant elevation in plasma level of both epinephrine (EPI) (P less than 0.02) and NE (P less than 0.001). Administration of 20 micrograms.kg-1 NX to six dogs resulted in immediate increases in HR (P less than 0.01) and MAP (P less than 0.01), and a further rise in CA levels to greater than pre-fentanyl baseline values. In six other dogs, NBPH (0.3 mg.kg-1) caused increases in HR (P less than 0.001) and MAP (P less than 0.001) only, and the MAP rise was significantly less than that seen in the NX group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of fentanyl reversal by naloxone at varying arterial carbon dioxide tensions in dogs.

Clinical reports, as well as animal studies, have described cardiovascular and sympathetic stimulation after the administration of naloxone (NX) to reverse opioid-induced respiratory depression. This investigation examines the effect of PaCO2 on hemodynamic and adrenergic responses to NX, by means of 24 experiments carried out in six dogs. Each dog underwent NX reversal of fentanyl (FEN) at three different PaCO2 levels: 20, 35, and 60 mm Hg. In a final series of six experiments, the dogs were exposed to increasing PaCO2 after autonomic block by total spinal anesthesia and vagotomy. During enflurane anesthesia, 50 micrograms/kg FEN decreased mean arterial blood pressure (MAP), heart rate (HR), and plasma concentrations of norepinephrine (NE) and epinephrine (EPI) significantly. NX 0.4 mg promptly returned HR and MAP to baseline or above in all experiments; catecholamine (CA) levels increased only in hypercapnic dogs. Increases in HR were the same in all series. MAP, EPI, and NE levels were significantly greater than pre-FEN baseline values only in hypercapnic dogs 1 minute after NX and were also significantly higher in hypercapnic than in hypocapnic dogs at this time. NE levels were greater in hypercapnic dogs at all time periods after NX. In blocked dogs, neither F nor NX had any effects on hemodynamic functions or plasma CA levels; the institution of hypercapnia caused significant decreases in HR, MAP, and systemic vascular resistance. This direct circulatory depressant action of an elevated PCO2 may have attenuated the indirectly mediated excitatory hemodynamic effects of NX in intact dogs, thus explaining the relatively greater effect of hypercapnia on adrenergic than on hemodynamic responses to reversal.(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine release by four narcotics: a double-blind study in humans.

Histamine release and hemodynamic changes associated with four narcotics were studied in 60 adults (28 men, 32 women) scheduled for general surgery under balanced anesthesia. Under double-blind conditions, incremental equipotent doses of meperidine, morphine, fentanyl, or sufentanil were administered IV for induction of anesthesia, prior to thiopental, succinylcholine, and intubation. Arterial blood samples were drawn before and 1, 6, and 20 min after narcotic administration. Of the 16 patients given meperidine (mean dose 4.3 +/- 0.2 (SEM) mg/kg), five (31%) had clinical signs (hypotension, tachycardia, erythema) and elevations in plasma histamine levels ranging from 3.2 to 49.7 ng/ml 1 min after narcotic administration. Plasma epinephrine levels at this time were also elevated in these five patients. One of the ten patients given morphine (0.6 +/- 0.02 mg/kg) developed hypotension, tachycardia, and an increase in plasma histamine level to 12.4 ng/ml. None of 34 patients given either fentanyl (7 +/- 0.4 micrograms/kg) or sufentanil (1.3 +/- 0.1 microgram/kg) had clinical signs of histamine release or elevations of plasma histamine levels. In the six patients in whom histamine release occurred, there was a significant correlation between the histamine levels at 1 min and the magnitude of change in heart rate, blood pressure, and plasma epinephrine level. All six histamine releasers were young women, ranging in age from 18 to 35 yr. Histamine release occurred more frequently after meperidine than after the other narcotics, including morphine, and the degree of hemodynamic compromise was related to the increase in plasma histamine concentration.

Reduced narcotic requirement by clonidine with improved hemodynamic and adrenergic stability in patients undergoing coronary bypass surgery.

The authors examined the effect of clonidine, a preferential alpha 2-adrenergic agonist, upon narcotic requirements, hemodynamics, and adrenergic responses during the perioperative period in patients undergoing CABG surgery. Anesthesia was provided by sufentanil supplemented with isoflurane; sodium nitroprusside was given as needed for hemodynamic control. Ten patients received oral clonidine preoperatively at the time of premedication, and again intraoperatively by nasogastric tube. Another group of ten untreated patients were otherwise managed identically. Intergroup differences in required anesthetic and vasoactive drug doses and recovery times were measured and evaluated, as well as hemodynamics and plasma catecholamines prior to induction, after intubation, and at intervals intra- and postoperatively. Patients who received clonidine required less diazepam prior to induction, and received 40% less sufentanil during the anesthetic period, than did untreated controls. More control patients required the addition of isoflurane to prevent hypertension. Mean blood pressures and heart rates were elevated at many sampling points in patients not treated with clonidine. Four of the clonidine-treated group required atropine for treatment of bradycardia in the pre-incision period. Plasma catecholamines were significantly lower throughout most of the study period in patients treated with clonidine. After cardiopulmonary bypass and postoperatively, cardiac outputs were significantly higher in the treated group. Patients who had received clonidine were extubated significantly earlier, and fewer of them shivered postoperatively. We conclude that perioperative treatment with clonidine reduced narcotic and anesthetic requirements, improved hemodynamics, reduced plasma catecholamines, and shortened the period of postoperative ventilation in patients undergoing coronary artery surgery.

Effects of fentanyl and diazepam in dogs deprived of autonomic tone.

In contrast to reports of the untoward hemodynamic effects of fentanyl and diazepam in intact organisms, we found that neither a bolus of 100 micrograms/kg fentanyl nor the addition of intravenous doses of diazepam, up to and including 1 mg/kg (cumulative dose 2 mg/kg) caused cardiovascular depression in 13 anesthetized dogs after elimination of their sympathetic and parasympathetic tone. There were no significant changes in mean arterial blood pressure, cardiac output, heart rate, peak left ventricular dP/dt, cardiac filling pressures, or systemic vascular resistance. Rapid bolus injection of 3 mg/kg diazepam (cumulative dose 5 mg/kg) caused a significant (P less than 0.05) but transient (time to 50% recovery less than 2 min) decrease in systemic vascular resistance, blood pressure, and dP/dt. When corrected for pressure changed (dP/dt divided by simultaneous left ventricular pressure), the decrease in dP/dt did not attain statistical significance, nor did changes in cardiac output or filling pressures, even after this large dose of diazepam. We conclude that previously reported decreases in hemodynamic function in subjects with intact autonomic function after fentanyl alone, or after the combination of fentanyl and diazepam, are indirect in nature, that is, are caused by a centrally mediated decrease in vasoregulatory (mainly sympathetic) outflow from the central nervous system.

Comparison of morphine, meperidine, fentanyl, and sufentanil in balanced anesthesia: a double-blind study.

A double-blind study comparing four narcotic analgesics of different potencies, meperidine, morphine, fentanyl, and sufentanil, was performed on consenting patients undergoing general or orthopedic surgery under balanced anesthesia. Blood pressure, measured through an indwelling arterial catheter, was recorded continuously, as were ECG and heart rates. The narcotics, made up in equipotent concentrations, were given as indicated by hemodynamic and clinical signs. Arterial blood samples were taken before and after induction, after intubation, before and after incision, at intervals during the operation, and postoperatively. Hemodynamic values and plasma levels of catecholamines during and after induction, intubation, incision, and throughout the operation were least in patients given sufentanil and greatest in those who received morphine or meperidine. Heart rates increased significantly after induction with meperidine and were significantly higher after intubation in morphine-treated and meperidine-treated patients than they were in patients receiving sufentanil. Intraoperatively, mean arterial blood pressure, rate-pressure product, and plasma norepinephrine levels were lowest in patients receiving sufentanil. Intraoperative plasma epinephrine levels were lowest in patients receiving sufentanil and meperidine. Because of increases in blood pressure, heart rate, or both to greater than 15% above control values, supplementation with a potent inhalational agent was necessary in 38%, 30%, and 29% of the patients given meperidine, morphine, and fentanyl, respectively. No sufentanil patient required supplementation. Side effects, including histamine release accompanied by tachycardia and hypotension, were most frequent and most severe in patients who received meperidine. After extubation, marked increases in heart rate, blood pressure, and plasma norepinephrine and epinephrine occurred in some patients in each group. The incidence of postoperative respiratory depression was greatest in patients given morphine (mean dose of naloxone 8.6 micrograms/kg) and least with sufentanil (mean dose of naloxone 1.8 micrograms/kg) and fentanyl (3.2 micrograms/kg naloxone).

Effects of fentanyl, naloxone, and clonidine on hemodynamics and plasma catecholamine levels in dogs.

A 50-micrograms/kg dose of fentanyl, given intravenously in divided doses to dogs under enflurane-nitrous oxide anesthesia caused sharp decreases in heart rate (HR), arterial blood pressure (AP), left ventricular dP/dt, and plasma levels of catecholamines. Naloxone, 20 micrograms/kg given 65-70 min later, completely and rapidly reversed these changes. Because the cardiovascular effects of fentanyl and naloxone occurred in unparalyzed animals under surgical anesthesia without eliciting any motor responses, it seems unlikely that they can be ascribed to changes in awareness and surgical stimulation, especially pain. The brief duration of exposure to the narcotic makes it improbable that the naloxone response is due to acute dependence and precipitated withdrawal. Pretreatment with 20 micrograms/kg of atropine only attenuated the decrease in HR, indicating a minor role of vagal mechanisms under these conditions. Administration of 20 micrograms/kg of clonidine by slow infusion after fentanyl further reduced sympathetic activity and greatly attenuated the naloxone response. Injection of 5 mg/kg of tolazoline after administration of clonidine produced massive cardiovascular stimulation by antagonizing clonidine and unmasking the naloxone reversal of fentanyl. Thus, in fully anesthetized dogs, fentanyl decreased the level of cardiovascular function mainly by reducing sympathetic activity. This effect does not seem to be secondary to analgesia or other sensory depressant effects of the narcotic, but rather to an action on central opioid-sensitive mechanisms regulating cardiovascular function.

Reflex responses to sodium nitroprusside and their control by cryptenamine.

In chloralose-anesthetized dogs the hypotensive and reflex cardiovascular responses to infusions of sodium nitroprusside were studied before and during halothane and enflurane, and before after divided doses of cryptenamine. The latter drug, a mixture of hypotensive veratrum alkaloids, lowers blood pressure reflexly by acting on afferent receptors (baroreceptors). Control infusions of nitroprusside, which caused 10% to 15% decreases im mean arterial blood pressure, markedly increased heart rate, myocardial contractility, cardiac output, rate-pressure product, and left ventricular minute work in spite of decreases in peripheral vascular resistance. Except for increases in contractility, these reflexly mediated effects were not blocked by the addition of 1% halothane or 2% enflurane. Cryptenamine, on the other hand, potentiated nitroprusside-induced hypotension, markedly diminished increases in heart rate, and eliminated increases in myocardial contractility, rate-pressure product, and left ventricular work. Measurements of cardiovascular function returned promptly to preinfusion values when the nitroprusside was stopped. We conclude that under conditions when a high degree of central vasomotor tone is present, homeostatic reflexes may counteract the direct vasodilator effect of nitroprusside, resulting in the need for a greater dose of nitroprusside and obviating the expected beneficial effects on myocardial oxygen supply/demand ratio. Combining cryptenamine with nitroprusside eliminates these problems and at the same time allows retention of the evanescent action of nitroprusside.

Sodium nitroprusside-induced hypotension for supine total hip replacement.

Deliberate hypotension was produced during general anesthesia by the infusion of sodium nitroprusside in 13 patients undergoing total hip replacement. Hemodynamic data from these patients were compared with those obtained from 5 patients under normotensive anesthesia for the same procedure. During the hypotensive period, which averaged 1.5 hours, the cardiac index rose 20 percent compared with controls. No acidotic tendency was seen. Blood loss in the study group averaged 475 ml, compared with 1475 ml in controls. From these data, a dose-response curve was derived which may allow the accurate prediction of the minute dosage of sodium nitroprusside required to safely induce hypotension during anesthesia.

A dosage nomogram for sodium nitroprusside-induced hypotension under anesthesia.

Sodium nitroprusside (SNP) was used to produce deliberate hypotension in 30 selected patients, 9 to 78 years of age, for total hip replacement under halothane-N2O-O2 anesthesia. Hypotension was induced in the first 13 patients by infusing a 0.01% (100 mug/ml) solution of nitroprusside (NP) in 5% dextrose. Blood pressure was diminished to a level just producing a dry surgical field. Preliminary data demonstrated that the mean arterial blood pressure (MAP) achieving this condition was 65 torr (p less than 0.01) and that the minute dosage of NP (mug/min) required to consistently reduce MAP to 65 torr could not be predicted on the basis of body weight. However, the age/weight ratio (yr/kg) of each patient, plotted against the known minute dosage of NP given during anesthesia, produced a highly significant dose-response curve (p less than 0.001, r = -0.8226). The preliminary dose-response curve was examined in a double-blind study on an additional 17 patients. The curve derived from the prospective study did not differ from that of the preliminary study. In addition, the combined data from the retrospective and prospective studies (30 patients) gave a better statistical fit than did those from the preliminary study alone (p less than 0.001, r = -0.8939). The nomogram provides an additional margin of safety in the use of this potent, fast-acting drug. SNP has been found predictable and effective in reducing surgical blood loss in selected patients undergoing total hip replacement.