An association between lung lymph endothelin concentration and survival during endotoxemia in awake sheep.

Endotoxin stimulates synthesis of endothelin which can cause pulmonary and systemic vasoconstriction and bronchoconstriction. Prolonged endotoxemia in sheep results in dramatic increases in pulmonary and systemic vascular resistances in nonsurvivors compared with survivors. Experiments were conducted in 12 conscious sheep (seven survivors, five nonsurvivors) to determine if synthesis of endothelin might contribute to the pathophysiology in nonsurvivors. Endotoxin was infused at 10 ng/min/kg for 12 h followed by a 4 h recovery in survivors. Lung lymph endothelin concentration peaked at 38.7 +/- 5.8 pg/mL during the endotoxin infusion in survivors compared with a peak of 128.7 +/- 33.0 pg/mL (p < .05) in nonsurvivors. Cardiac output was lower, and systemic and pulmonary vascular resistances and the Aa gradient in PO2 were significantly greater in nonsurvivors compared with survivors. These variables are those likely to be affected by increased circulating endothelin concentrations which suggests that endothelin contributes to early mortality during prolonged endotoxemia.

Catheter embolization following median sternotomy.

A case of intraoperative internal jugular vein catheter embolization in a patient undergoing median sternotomy for open-heart surgery is described. This complication suggests that right sided cannulation of the internal jugular vein is to be preferred in all patients having a median sternotomy in order to avoid the risk of intersection by median sternotomy.

Loss of endothelium-dependent vasodilation in the pulmonary vessels of sheep after prolonged endotoxin.

We examined the hemodynamic response of awake sheep to prolonged endotoxin infusion (10 ng.kg-1 x min-1 for 12 h) and the in vitro endothelium-dependent relaxation of pulmonary arterial vessels excised 12 h after the end of endotoxin infusion to determine whether the development of pulmonary hypertension after endotoxin is associated with loss of endothelium-dependent relaxation. In seven of nine sheep, there was a maintained increase (4-68% of baseline) in pulmonary arterial pressure 24 h after the beginning of endotoxin infusion. The greater the increase in pulmonary arterial pressure in vivo, the greater was the in vitro deficit in endothelium-dependent relaxation of the pulmonary vessels. The maximum in vitro vessel dilation was 59% for pulmonary artery rings isolated from sheep without a sustained increase in pulmonary arterial pressure 24 h after endotoxin. Prolonged endotoxin infusion did not alter the in vitro response of pulmonary arterial vessels to KCl or 10(-5) M norepinephrine. Force development, response to 10(-5) M norepinephrine, and vasodilation in response to acetylcholine were also not altered in pulmonary vessels taken from control sheep and exposed in vitro to tumor necrosis factor-alpha (400 U/ml). Our results suggest that loss of endothelium-dependent relaxation in pulmonary vessels supports the sustained pulmonary hypertension that develops after prolonged exposure to endotoxin.

Plasma tumor necrosis factor-alpha during long-term endotoxemia in awake sheep.

We used a continuous 12-h infusion of Escherichia coli endotoxin (10 ng.min-1.kg-1) in 10 awake sheep equipped with a lung lymph fistula and vascular catheters to determine the time course of increased plasma tumor necrosis factor-alpha (TNF-alpha) during the infusion and a 12-h postinfusion period. Lung lymph flow increased progressively during the infusion to a peak value averaging 8.6 +/- 2.0 times the baseline flow of 6.3 +/- 1.3 g/h. During the postinfusion period, lung lymph flow remained elevated at three to four times baseline. The lymph-to-plasma protein concentration ratio was unchanged from baseline over 24 h, indicating a dramatic increase in net protein flux across pulmonary microvessels. The TNF-alpha concentration peaked early in the infusion and then declined, despite the continuing presence of endotoxin. Plasma TNF-alpha concentration increased 10-fold (0.33 +/- 0.05 ng/ml at baseline to 3.89 +/- 0.78 ng/ml peak) 2 h into the endotoxin infusion. At the end of the endotoxin infusion, plasma TNF-alpha had decreased to 1.16 +/- 0.19 ng/ml. The circulating TNF-alpha concentration did not correlate with pathophysiology or outcome in these sheep.

TNF-alpha and the pathophysiology of endotoxin-induced acute respiratory failure in sheep.

We studied changes in cardiovascular and pulmonary function during prolonged endotoxemia in conscious sheep. Sheep with chronic lung lymph fistulas received a 12-h infusion of Escherichia coli endotoxin (10 ng x kg-1 x min-1) and allowed to recover for 12 h. Supportive therapies were withheld. Prolonged endotoxemia without volume support caused systemic hypotension associated with reduced cardiac output and increased systemic vascular resistance, pulmonary hypertension, and acute lung injury with progressive respiratory failure. Plasma tumor necrosis factor-alpha (TNF-alpha) concentrations increased transiently. Sustained pulmonary hypertension and increased pulmonary and systemic vascular resistances contributed to a poor outcome in 9 of 34 sheep (26%). Plasma TNF-alpha concentrations were significantly greater in survivors with sustained pulmonary hypertension and in nonsurviving sheep than in surviving sheep without pulmonary hypertension. Endotoxin (1 ng/ml) increased neutrophil expression of TNF-alpha in vitro. Addition of interleukin-6 prevented this response. Synthesis and release of TNF-alpha may be an important proximal event influencing the development of sustained pulmonary hypertension and progressive respiratory failure with endotoxemia. Interleukin-6 may contribute to the phasic nature of the TNF-alpha response.

Interaction between naloxone and serotonin in the control of the cardiovascular system in hemorrhaged cats.

We investigated the mechanism for the pressor effect of intravenous administration of naloxone in pentobarbital-anesthetized cats. Comparisons were made between groups of hemorrhaged animals that received either naloxone or an equivalent volume of saline after 1 h of hemorrhage. Two other groups of hemorrhaged animals were depleted of serotonin by pretreatment with para-chlorophenylalanine 40-48 h before the experiment. One group of serotonin-depleted animals received naloxone after 60 min of hemorrhage and the other group received saline. Animals with normal brain serotonin content showed a significant pressor effect following naloxone when compared with animals given saline. Animals with reduced brain serotonin content also had a pressor response following naloxone administration. Serotonin-depleted animals showed an increase in maximum left ventricular dP/dt following naloxone administration when compared to serotonin-depleted animals given saline. Our data are consistent with the hypothesis that naloxone can exert a pressor effect in hemorrhaged cats by actions at central and at peripheral sites. In cats with normal serotonin values, the peripheral action of naloxone is predominant. In serotonin-depleted animals given naloxone, central and peripheral sites contribute to the pressor effect.

Feeding patterns of three sympatric tsetse species (Glossina spp.) (Diptera: Glossinidae) in the preforest zone of Côte d'Ivoire.

The feeding patterns of Glossina longipalpis Wiedemann 1830, G. medicorum Austen 1911, G. palpalis gambiensis Vanderplank 1949 and G. p. palpalis Robineau-Desvoidy 1830 are described from natural habitats in central Côte d'Ivoire where these tsetse species occurred sympatrically. Blood-meal identification of tsetse flies revealed that in natural habitats wild ruminants were by far the most frequent source of food for each Glossina species, but there were significant differences between the nutritional spectra of single fly species. G. p. gambiensis fed significantly less often on bushbuck and significantly more often on monitor lizard (Varamus niloticus) than both, G. longipalpis and G. medicorum. In G. p. gambiensis the blood of wild ruminant species was significantly more often found than in G. p. palpalis, whereas the latter fed significantly more often on domestic animals. Peridomestic populations of G. longipalpis and G. p. palpalis fed mostly on domestic pig and therefore had significantly reduced host spectra in comparison to natural populations. The significant differences in feeding patterns among the investigated species, subspecies and populations seem not to depend on species specific feeding preferences. Rather, they can be attributed to microhabitat specialization of the various tsetse groups and hence mainly to the different availability of hosts. This implies that environmental factors should be taken more into account when analysing and comparing the feeding patterns of tsetse.

Natural host odours as possible attractants for Glossina tachinoides and G. longipalpis (Diptera: Glossinidae).

As strictly haematophagous insects, tsetse flies feed on a wide variety of wild and domestic animals. Although these are mainly mammals, some tsetse species also feed on reptiles. The present study investigated whether the odours of several potential natural tsetse hosts may be used as novel attractants to improve the catch of Glossina tachinoides or G. longipalpis in biconical traps. The odour of a living monitor lizard (Varanus niloticus) had no effect on the catch of G. tachinoides. Hexane skin washings of monitor lizard and warthog (Phacochoerus aethiopicus) dispensed in small quantities improved the catch of G. tachinoides significantly by factors of up to 1.34 and 1.46, respectively. Skin washing of bushbuck (Tragelaphus scriptus) did not increase the catch of G. tachinoides, but the synthetic phenolic fraction of bushbuck urine enhanced it significantly by 1.81 times. The catch of G. longipalpis was improved significantly by the urines of warthog, domestic pig and bushbuck by factors of 1.58, 1.91 and 2.51, respectively. In relation to the quantity of evaporated odour, bushbuck and warthog urine seem to be of particular interest for further attractant studies. The effect of tested host odours on the catch of G. tachinoides and G. longipalpis is compared with data of other tsetse species and with the frequency these hosts are fed on by tsetse flies. Bushbuck is one of the principal natural hosts of both Glossina species investigated, and of all odours tested, bushbuck urine and its synthetic phenolic fraction improved the catch of both tsetse species the most.

New cineromycins and musacins obtained by metabolite pattern analysis of Streptomyces griseoviridis (FH-S 1832). II. Structure elucidation.

A detailed analysis of the secondary metabolite pattern produced by Streptomyces griseoviridis (strain FH-S 1832) using a chemical screening method resulted in the detection, isolation and structure elucidation of new 14-membered lactones of the cineromycin B-type [dehydrocineromycin B (5), oxycineromycin B (7), and 2,3-dihydrocineromycin B (8)], as well as new gamma-lactones related to nigrosporalactone and 4,5-dihydroxy-octa-2,6-dienoic acid esters named musacins A to F (10, 13 approximately 15, 17, 18 and 21). The constitution of these metabolites were deduced from spectroscopic data as well as chemical transformations. The configuration of musacin D (10) was determined by derivatization with chiral acids (Helmchen's method).

Olfactory attractants for West African tsetse flies, glossina spp. (Diptera: Glossinidae).

The effect of various natural host odours on Glossina longipalpis, G. medicorum and G. tachinoides from catches in odour-baited biconical traps was analysed. Substances tested were ox urine, and the eight components of its phenolic fraction, as well as acetone and 1-octen-3-ol, both of which are present in ox breath. Ox urine increased the catch of G. tachinoides significantly by 1.2 times. Its phenolic fraction gave increases of up to 1.6 for G. longipalpis and 1.4 for G. tachinoides (significant in both cases). Adding acetone and/or 1-octen-3-ol to the phenolic fraction increased attraction of G. longipalpis and G. tachinoides significantly by up to 1.8 and 1.3 times, respectively. Octenol on its own increased the catch of all three species significantly by up to 2.2 times. Acetone alone, in combination with octenol or with the phenolic fraction reduced the catch of G. medicorum significantly to a level of 0.2. 3-Methylphenol and 4-methylphenol are those components of the phenolic fraction which showed the highest attractiveness on tsetse flies in the experiments. Several mixtures of both methylphenols and/or 1-octen-3-ol were tested as attractants for all three tsetse species.

Pericardial tamponade-induced myocardial ischemic injury.

Cats of either sex anesthetized with sodium pentobarbital (30 mg/kg, IV) were subjected to sham pericardial tamponade or pericardial tamponade for five hours. Five cats underwent sham pericardial tamponade and six cats were subjected to pericardial tamponade which reduced the mean arterial blood pressure to approximately 40 mm Hg. Pericardial tamponade produced a 44-51% and a 28-38% decrease in the myocardial activities of cathepsin D and creatine phosphokinase (CPK), respectively. Observation of cellular and subcellular structure of left ventricular tissue of two sham operated cats and two cats after tamponade revealed myocardial injury in cats subjected to tamponade. Tissue stained with hematoxylin-basic fuchsin-picric acid stain showed extensive crimson-red basic fuchsin staining in cats subjected to pericardial tamponade and the absence of staining in cardiac tissue of sham-operated cats. Electron micrographs of cardiac tissue of cats subjected to acute pericardial tamponade revealed extensive vacuolization and extreme contracture. These results indicate ischemic injury with loss of cellular and subcellular enzymes in hearts of cats after five hours of pericardial tamponade sufficient to reduce the mean arterial blood pressure to about 40 mm Hg.

Pancreatic hypoperfusion and the production of a myocardial depressant factor in hemorrhagic shock.

Hemorrhagic shock was produced in dogs by bleeding to a systemic blood pressure of 45 mm Hg for 3 hours, followed by reinfusion of the shed blood. A rapid decrease in pancreatic blood flow occurred and pancreatic perfusion remained at 15-25% of control over the entire 3-hour oligemic period. As a consequence of this marked degree of pancreatic hypoperfusion, autolytic changes occurred in pancreatic acinar cell ultrastructure, particularly in the enlarging of lysosomes which developed many vacuoles. Plasma proteolytic indices (e.g., cathepsin D activity and amino nitrogen concentration) markedly increased during shock as well as the activity of a myocardial depressant factor (MDF). MDF was also produced in incubated pancreatic homogenates obtained from nonshocked dogs and in non-incubated homogenates from shocked dogs. MDF activity in the homogenates was closely correlated with amino nitrogen concentration. These data suggest that pancreatic hypoperfusion plays a key role in MDF formation and ultimately in the pathogenesis of circulatory shock. Moreover, MDF activity was found not to be associated either with pentobarbital concentration or the salt content of active fractions of plasma and pancreatic tissue. Ashing of active fractions was very effective in destroying MDF activity. These data are consistent with the earlier findings that indicate MDF to be a peptide having a molecular weight of 500-1,000.

Effects of dexamethasone on myocardial cells in the early phase of acute myocardial infarction.

Dexamethasone exerted no significant hemodynamic effect in sham-operated cats or in cats subjected to acute myocardial ischemia. However, the glucoccortcoid did normalize elevated S-T segments toward pre-ischemic values, and prevented much of the increase in plasma CPK activity following coronary artery ligation. Moreover, dexamethasone prevented loss of CPK activity and restricted the loss of lysosomal hydrolase within ischemic myocardial tissue. These data indicate that lysosomal disruption is an early consequence of myocardial ischemia and that treatment with dexamethasone prevents the loss of myocardial lysosomal and cellular enzymes as reflected in normalization of the ECG and plasma CPK activity of ischemic cats. In this way, dexamethasone may act to retard the spread of the developing infarct within the ischemic myocardium.

Blood flow and ultrastructure in ischemic myocardium of cats given dexamethasone.

Regional myocardial blood flow or myocardial creatine kinase activity and ultrastructure was studied in anesthetized cats subjected to sham operation, 5 h of circumflex-artery ligation, or 2 h of coronary-artery ligation with 3 h of reperfusion. Sham-operated cats were given dexamethasone sodium phosphate (8 mg/kg iv) at the beginning of the experiment. Cats subjected to coronary-artery ligation were given steroid or vehicle before ligation. In sham-operated cats the average blood flow in tissue of the anterior wall was 2.11 +/- 0.37 (SER) ml.g-1.min-1. The corresponding flow for tissue of the posterior wall was 2.22 +/- 0.42 ml.g-1.min-1. Ligation of the circumflex artery produced a range of average blood flow in the posterior basal myocardium that was 52-92% less than that of sham-operated cats. Within the tissue of the posterior left ventricular wall, steroid pretreatment did not prevent loss of creatine kinase activity after coronary-artery ligation. Moreover, steroid pretreatment was ineffective in maintaining myocardial structure in reperfused myocardial tissue. These results indicate that 1) dexamethasone does not effectively increase blood flow within ischemic or reperfused myocardial tissue, and 2) dexamethasone may stabilize ischemic myocardial tissue. However, upon reperfusion, dexamethasone is unable to maintain myocardial ultrastructure in moderately to severely ischemic tissue.

[Cochlear potentials and reduced blood supply]. / Kochleapotentiale und Mangeldurchblutung.

In cats the mean arterial blood pressure (MABP) was reduced to 40 or 30 mm Hg by controlled hemorrhage. In 3 animals the cochlea action potentials (CAP) are not changed between 30 and 380 Min by 40 mm Hg MABP. In 4 animals we saw a latent or permanent decrease of CAP between 4 and 115 Min by 30 mm Hg MABP. A singular experiment shows, that a CAP-decrease is caused by injection of an acetylcholin blockade substance. We did not find a correlation to the length of time of the ischemia and a CAP decrease. We found an exact correlation to the hypovolemic sympathetic palsy and a CAP decrease. In reduced blood perfusion the cochlea of cats is more resistant than the brain.

Interaction of supraspinal, serotonergic, and opiate systems during hemorrhage.

Anesthetized cats were subjected to hemorrhage to a mean arterial blood pressure of 40 +/- 1 mmHg. After 60 min of oligemia pressure regulation was stopped, and naloxone hydrochloride or an equivalent volume of 0.9% saline was given intravenously as a bolus (2 mg x kg-1) followed by a continuous infusion (2 mg x kg-1 x hr-1). In other cats supraspinal systems were ablated by functional decapitation (FD) or serotonergic systems were ablated by IP injection of parachlorophenylalanine (pCPA, 300 mg/kg, 48 h prior to hemorrhage). Cats subjected to ablation of supraspinal or serotonergic neurons showed a distinct pressor response after naloxone. Although cats with intact neuronal systems failed to show a distinct pressor response to naloxone, the arterial pressures of these cats were significantly greater than hemorrhaged cats given saline (P less than 0.05, unpaired t). Our results suggest that a supraspinal system and a serotonergic system can interact to limit the pressor response to naloxone in hemorrhagic shock.

Extravascular water content of heart and lungs after acute myocardial ischemia.

We measured the extravascular water content of hearts and lungs of anesthetized dogs subjected to one of the following protocols: a)sham operation, b) circumflex artery ligation, c) increased left atrial pressure (Pla), or d) increased Pla and circumflex artery ligation. After 4 h, extravascular water of the heart and lungs increased significantly in the three experimental groups when compared with values from sham-operated dogs. After circumflex artery ligation, extravascular heart water increased 29% and lung water 8%, although Pla and calculated pulmonary microvascular pressure (Pmv) did not change. Extravascular heart water also rose 30% after increasing Pla from 23 to 37 cm H2O by inflating a left atrial baloon. In these dogs, extravascular lung water increased as a hyperbolic function of Pmv. Increasing Pla to 20 cm H2O in dogs with coronary artery ligation resulted in a 16% increase in heart water. Also at each Pmv, extravascular lung water was greater in dogs with coronary artery ligation than in dogs without. These data indicate that the increased extravascular lung water after coronary artery ligation cannot be explained solely by hemodynamic mechansims. We suggest that acute myocardial ischemia contributes to an increase in vascular permeability in the heart and lungs.

Influence of increased circulating levels of splanchnic lysosomal enzymes on the response to myocardial ischemia.

The ability of increased circulating activities of lysosomal hydrolases to disrupt myocardial cellular membranes was studied in anesthetized cats. Increased activities of lysosomal hydrolases were achieved by splanchnic artery occlusion (SAO) shock or by infusion of liver extract (LE). Myocardial ischemia (MI) was produced by ligation of the left coronary artery. Coronary artery ligation resulted in sustained S-T segment elevation associated with significant increases in plasma creatine phosphokinase (CPK) activity within 5 hours. Combinations of SAO or LE infusion did not modify the increase in either the plasma CPK activity or the S-T segment following MI. However, SAO shock or infusion of LE increased CPK loss from normal and ischemic myocardium, the loss being greater when MI was combined with infusion of LE or SAO shock. Similarly, MI plus SAO shock increased the loss of the lysosomal protease cathepsin D from normal and ischemic myocardial tissue. Moreover, cats subjected to MI and given LE inhibited increased mortality and decreased clearance of infused lysosomal hydrolases. These results indicate that conditions affecting increased plasma levels of hydrolases promote increased disruption of normal and ischemic myocardial tissue. These findings are consistent with the concept that hydrolases originating in the splanchnic viscera during shock play a role in enhancing damage to normal and ischemic myocardial tissue following coronary artery occlusion.