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Progressive hemorrhage in the absence of tissue injury produces a biphasic response: an initial tachycardia, vasoconstriction and maintenance of arterial blood pressure by the baroreflex, followed by bradycardia, vasodilatation and hypotension due to the activation of a second 'depressor' reflex. The present study has investigated the effect of morphine (a mu-opioid receptor agonist) on the cardiac chronotropic response to a progressive hemorrhage at 2% total estimated blood volume (BV) min(-1) in the anesthetized rat. In control rats (20 microl saline intracerebroventricularly, i.c.v.) heart period initially decreased significantly (P < 0.05) by a maximum of 5.4 +/- 0.8 ms from a baseline of 147.3 +/- 2.2 ms after a blood loss of 8.3 +/- 1.5% BV, and then increased significantly by a maximum of 43.0 +/- 5.5 ms above the baseline after the loss of 34.5 +/- 1.6% BV. Blood pressure was initially maintained and then fell during the hemorrhage. The increase in heart period was prevented by treatment with morphine (10 microg i.c.v.), and the fall in blood pressure delayed significantly. These effects of morphine were prevented by pretreatment with naloxone (20 microg i.c.v.). Intravenous (i.v.) administration of morphine (10 microg) had no effect on the response to hemorrhage. However, a clinically relevant dose of 0.5 mg x kg(-1) morphine (i.v.) abolished the bradycardia and delayed the fall in blood pressure associated with hemorrhage. These results indicate that morphine, acting on central nervous opioid receptors, can abolish the bradycardia and delay the hypotension associated with progressive hemorrhage, a pattern of response reminiscent of the effects of musculo-skeletal injury on the response to blood loss.

Background: Although both genetic and nongenetic factors contribute to the pathogenesis of coronary artery disease, the identification of specific genetic lesions has lagged behind the identification of critical environmental risk factors. A reported association between myocardial infarction (MI) and the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in European men suggests a critical role for this genomic region. However, the generality of this association remains to be determined. It also is not clear at what stage in disease progression the association with the ACE I/D polymorphism becomes important., Methods and Results: We evaluated the ACE I/D polymorphism in patients who had undergone coronary angiography (402 men and 295 women) and in 203 representative control subjects. After polymerase chain reaction amplification, genotypes were determined by agarose gel sizing and by hybridization with allele-specific oligonucleotides. After patients were categorized by the degree of coronary artery stenosis and the occurrence of an MI, the distribution of ACE I/D genotypes was evaluated by log linear analysis. Patients were genetically representative of the regional population, and patients with > 60% stenosis of their coronary arteries had the same distribution of ACE I/D genotypes as did patients with < 10% stenosis. However, among patients with stenosis, the occurrence of an MI was significantly associated with the D allele in all patients (odds ratio [OR], 1.59; P = .002) and in men alone (OR, 1.63; P = .006). The lack of significance in women (OR, 1.40; P = .263) is probably due to the fact that only 36 women in the present study had experienced an MI. Furthermore, the association between MI and the ACE I/D polymorphism was independent of blood pressure, smoking habits, and body mass index., Conclusions: Segregation of the ACE I/D polymorphism is a pervasive genetic risk factor for MI in whites but has no evident effect on the events leading to stenosis of the coronary arteries. This suggests that risk of MI is influenced by two independent processes--atherogenesis that leads to coronary stenosis followed by conversion to MI. The renin-angiotensin system appears to confer significant risk of infarction by influencing the conversion to MI but has no apparent effect on the development of atherostenosis.

Background: Because genetic factors are believed to contribute to the etiology of coronary artery disease (CAD), it has been suggested that DNA polymorphisms at candidate loci might identify individuals at high risk for developing disease. In this regard, apolipoprotein genes represent extremely promising loci because levels of apolipoproteins and their associated lipoproteins represent a major risk factor for CAD, and rare dysfunctional mutations in these genes result in a significant risk for CAD. To date, although some reports indicate that DNA polymorphisms at these loci are associated with increased risk of CAD, other reports have failed to find such associations., Methods and Results: To resolve the question of whether genetic polymorphisms at apolipoprotein loci can be used to identify individuals at increased risk for CAD, we evaluated the distribution of apolipoprotein genetic polymorphisms in a large series of subjects (n = 848) undergoing coronary angiography. Blinded assessment of angiograms was used to discriminate between patients with CAD (> or = 60% stenosis of any major branch, n = 444) and control subjects without disease (< or = 10% stenosis, n = 404). A total of 12 polymorphisms were evaluated at the following loci: apolipoprotein (apo) A-I/C-III/A-IV (five restriction site polymorphisms--Msp I, Pst I, Sst I, Pvu IIa, Pvu IIb), apo B (three restriction site polymorphisms--Xba I, EcoRI, Msp I, plus an insertion/deletion polymorphism), apo A-II (Msp I polymorphism), apo C-II (Taq I polymorphism), and apo E (protein isoforms revealed by DNA analysis). All subjects were of Northern European (primarily Angloscandinavian) descent, and, within each sex, patients and control subjects were of comparable age. All 12 loci were in Hardy-Weinberg equilibrium, with no indication of population heterogeneity. As expected, patients were distinguished from control subjects by their lipid profiles and a higher frequency of known risk factors for CAD. However, analysis by log-linear models indicated that there were no significant associations between apolipoprotein polymorphisms and the risk of CAD (P = .10 to .90). The lack of association was maintained irrespective of whether the analysis was carried out for the entire sample or the contrast was made more stringent by comparing patients most likely to have a genetic component to their disease (ie, young patients with early-onset CAD) with the control subjects least likely to have genetic susceptibility (ie, older control subjects who had ample time to develop CAD)., Conclusions: Despite the fundamental role of apolipoprotein genes in lipid metabolism, we find no evidence that common genetic polymorphisms of the major apolipoprotein loci have a significant influence on the risk of developing angiographically defined CAD in this representative population. Therefore, at this time we find no support for the hypothesis that mass screening for genetic polymorphisms at candidate loci can reduce the burden of CAD by identifying a substantial proportion of high-risk individuals. Instead, it appears more appropriate to direct attention toward modifying high-risk behaviors to alleviate the consequences of traditional environmental risk factors.

Objective: To quantitatively define the coronary vascular bed in the 21-day-old rat fetus with gestational normoxia and hypoxia; to determine if maternal supplemental oxygen and/or oxygen-carrying perfluorocarbons (PFCs) influence development of coronary vessels; and to compare the results using purified and unpurified PFC treatment., Design: Unilateral uterine artery ligation was introduced on gestational day 17 in pregnant animals. Control fetuses were from unligated uterine horns. Experimental intervention occurred during gestational days 17 to 21, with fetuses recovered on day 21. Developing coronary vessels were analyzed quantitatively via light microscopy., Animals: Pregnant Sprague Dawley rats., Interventions: Following ligation, pregnant rats received no further treatment, supplemental oxygen inhalation alone, or daily intravenous purified PFC treatment, with or without supplemental oxygen., Main Results: Hypoxia caused an increase in resorptions (P less than 0.001), and decreased fetal body weight (P less than 0.001) and heart weight (P less than 0.05). Although the area occupied by developing coronary vessels (sinusoids) was substantially increased, maturation was unchanged. Oxygen supplementation alone did not appreciably influence fetal resorptions or body weight in ligated horns, but did increase fetal heart weight. Sinusoidal area decreased (P less than 0.01), with no effect on sinusoidal maturity. Purified PFC treatment did not alter maternal weight gain or fetal body weight, and moderately decreased resorptions in ligated horns. Fetal heart weight was augmented with purified perflurochemical, while unpurified perfluorochemical treatment diminished heart weight. Both PFC emulsions substantially decreased sinusoidal area., Conclusions: Perflurocarbon treatment associated with supplemental oxygen is capable of improving the hypoxic effects on fetal heart and coronary vessel development if the emulsion used is appropriately purified.

A moderate haemorrhage of 0.75 +/- 0.09 ml (100 g body weight)-1 (11.1 +/- 1.3% of estimated blood volume) in the conscious rat produces a tachycardia, possibly mediated by the baroreflex, which serves to maintain mean arterial blood pressure. A severe haemorrhage of 1.20 +/- 0.06 ml (100 g)-1 (greater than or equal to 19.5 +/- 1.5% of estimated blood volume) produces a bradycardia and marked hypotension. The bradycardia is reflex in nature and is due to an increased vagal efferent activity to the heart. This bradycardia is markedly attenuated in animals treated neonatally with capsaicin to render them deficient in C fibres, suggesting that peripheral C fibres (possibly cardiac C fibre afferents, Oberg & Thorén, 1972) are of importance in the bradycardic response to a severe haemorrhage. Concomitant tissue injury produced by bilateral hindlimb ischaemia in a group of animals with normal C fibre afferents markedly attenuates or abolishes the bradycardia and reduces the fall in mean arterial blood pressure produced by severe haemorrhage, although the tachycardia seen with smaller haemorrhages is affected to a much lesser degree. It is concluded that tissue injury can modify the cardiovascular response to a severe haemorrhage, possibly by interacting with the reflex effects of stimulating cardiac C fibre afferents.

The effect on the inhibition of shivering by limb ischaemia of small 6-hydroxydopamine (6-OHDA) lesions in the hypothalamus has been studied in rats. The injection of 6-OHDA into the posterior part of the hypothalamus in the neighbourhood of the N. dorsomedialis or into the ventral ascending catecholaminergic bundle caudal to that nucleus prevented the depression of the ambient temperature threshold for the onset of shivering which usually occurs during hind-limb ischaemia and lowered the slope of the regression line relating the intensity of shivering to ambient temperature. In rats not treated with 6-OHDA this slope is unaffected by limb ischaemia. These lesions reproduced the changes seen when 6-OHDA was injected into the lateral cerebral ventricle. Lesions in other parts of the hypothalamus were without effect. It is concluded that the inhibitory catecholaminergic synapses are situated in the posterior part of the hypothalamus and that the impulses reach them from nerve cells in the hind-brain via the ventral bundle. The lesions produced in these experiments had little effect on thermoregulation in non-injured rats.

Fifty patients with acute myocardial infarction were randomly assigned to receive either intracoronary streptokinase or standard (control) therapy within about three hours after the onset of pain. Coronary perfusion was reestablished in 19 of 24 patients receiving streptokinase. Streptokinase alleviated pain (as indicated by differences in subsequent morphine use). The Killip class was significantly improved after therapy with streptokinase, as were changes in radionuclide ejection fraction between Days 1 and 10 in surviving patients (+3.9 vs. -3.0 per cent, P less than 0.01). The echocardiographic wall-motion index also showed greater improvement after streptokinase treatment (P less than 0.01). Streptokinase therapy was associated with rapid evolution of electrocardiographic changes, which were essentially complete within three hours after therapy, but loss of R waves, ST elevation, and development of Q waves in the convalescent period were greater in the control group (P less than 0.01). The time required to reach peak plasma enzyme concentrations was significantly shorter after streptokinase. The incidence of early and late ventricular arrhythmias was not affected by treatment. We conclude that intracoronary streptokinase appears to have a beneficial effect on the early course of acute myocardial infarction.

The effects of bilateral hind-limb ischaemia on blood pressure and on the blood pressure-heart rate reflex have been studied in the rat. Limb ischaemia increased blood pressure and decreased the elevation and slope of the regression line describing the relationship between heart period (H.P.) and mean arterial pressure (M.A.P.). Nociceptive afferents from muscle receptors using long fibre tracts in the anterolateral part of the spinal cord seem to be responsible for the changes seen. The changes in the blood pressure-heart rate reflex were mediated by a combination of vagal inhibition and sympathetic activation. The efferent pathway for the pressor effect was in the sympathetic outflow. Central catecholaminergic neurones were involved in the pressor effect of limb ischaemia but not in the changes in the blood pressure-heart rate reflex. Electrolytic lesions in the posterior hypothalamus attenuated the inhibition of the reflex and it is suggested that neurones in the defence area may be activated by limb ischaemia. The interaction between limb ischaemia and the H.P.-M.A.P. relationship was not affected by opioid antagonists. After the period of ischaemia there was an increase in the elevation of the regression line describing the relationship between H.P. and M.A.P. which was secondary to the fall in body temperature characteristic of this phase of the response to injury.

Intracoronary streptokinase (SK) may have beneficial effects on the in-hospital course of acute myocardial infarction (MI), but long-term outcome is unknown. We evaluated the outpatient course of 50 MI patients, randomly treated with either SK (n = 24) or standard therapy (n = 26), who presented within 2.7 +/- 0.7 hours of symptoms. Coronary reperfusion occurred in 19 (79%) SK patients. Survivors were followed for a mean of 18.7 months (range 11 to 28.5); information was current in 48 patients (96%). Both groups received antiplatelet therapy for 3 months. A total of five deaths occurred in the control group and two in the SK group, including one posthospital death in each. Nonfatal MIs totaled five in control patients and three in SK patients, including five posthospital MIs (three control, one SK). Differences in major events (death or nonfatal MI) favoring SK did not quite reach statistical significance (10 control vs 5 SK). Bypass surgery was performed in seven SK and four control patients (NS). Angina occurred in more control (15) than SK (six) patients (p less than 0.01), and more control patients used long-acting nitrates (14 control, three SK; p less than 0.01). Palpitations were noted by nine control and one SK patient (p less than 0.01), and documented late arrhythmias were present in four control patients and no SK survivors (p less than 0.05). Symptoms suggestive of heart failure were present in seven control and one SK patient (p less than 0.01); two control patients were hospitalized for failure. Use of beta blockers, calcium channel blockers, and other cardiac medications did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

An attempt has been made to assess the effect of injury (limb ischaemia, scald) on the central serotoninergic system of the rat by studying the effect of these injuries on the tryptophan concentration, the tryptophan hydroxylase activity and the metabolism of serotonin in the hypothalamus, mid-brain and hind-brain. The effects of a serotonin uptake inhibitor and an antagonist on the survival time and mortality rate after limb ischaemia have been examined as well as the effects of central lesions produced by the injection of 5.6- and 5.7-dihydroxytryptamine into a lateral cerebral ventricle and the i.p. injection of (+/-)-4-chloroamphetamine. A few changes indicative of increased activity in the central serotoninergic system were found--an increase in tryptophan hydroxylase activity after 4 h bilateral hind-limb ischaemia, better survival of fed rats pre-treated with 5,6-dihydroxytryptamine--but for the most part the changes were not as great as those produced by starving or exposure to cold. Hence the effect of trauma on this system seems small.

1. A rise or a fall in systemic blood pressure brought about by the I.V. infusion of peripherally acting drugs (adenosine, noradrenaline or methoxamine) inhibited shivering in the cold-exposed rat. 2. Since the injection of commonly used doses of noradrenaline (0.05-0.10 mumole) into a lateral cerebral ventricle of a rat was usually accompanied by a rise in blood pressure special precautious were required to determine whether noradrenaline had a specific central effect on shivering. 3. Small doses of noradrenaline (0.02-0.03 mumole) or clonidine (0.01 mumole) which had no effect on blood pressure when injected into a lateral cerebral ventricle still inhibited shivering in the cold-exposed rat and this effect was prevented by phentolamine. 4. It is concluded that noradrenaline can inhibit the cold sensor-shivering pathway in its central course by an action on alpha-receptors.

1. Dopamine (0.5--0.2 mumole) injected into a lateral cerebral ventricle inhibited shivering and lowered core temperature in rats at an ambient temperature of 0--5 degrees C. 2. These effects were inhibited by the dopamine antagonist, pimozide, and imitated by the dopamine agonists, piribedil and apomorphine. 3. Pimozide itself had no effect on shivering. 4. It is concluded that while there are inhibitory dopamine receptors on the cold sensor--shivering pathway in the rat they are not concerned in the normal function of this pathway.

The effects of two components of tissue injury, namely fluid loss from the circulation and tissue ischaemia, on cardiovascular reflex activity have been studied. Moderate blood loss (10-20% blood volume) in the unanaesthetized rat increased the slope of the regression line relating heart period to mean arterial blood pressure and usually displaced it to the left (i.e. towards a relative bradycardia). A blood donation of 500 ml (approximately 10% blood volume) increased the Valsalva ratio in conscious man without a change in resting pulse rate. However, a 15 min period of unilateral limb ischaemia in man reduced the Valsalva ratio. The pattern of change in the pulse rat response to the Valsalva manoeuvre produced by limb ischaemia closely resembles that found previously after limb injury in man. There was no evidence that the endogenous opioids were involved in the interaction between limb ischaemia and cardiovascular reflex activity in man.

The sequence for the onset of segmental contraction of the left ventricle was studied in 25 normal patients by analyzing sequential frames obtained at 16.7-msec intervals of right anterior oblique (RAO) ventriculograms by two independent methods. In the first method, we compared the times of onset of contraction of the hemidiameters associated with each of 54 segments with time of onset of contraction of the average of all the hemidiameters for the ventricular contour. In the second method we used a radial coordinate system and determined relative phase relationships by plotting the motion of each of 54 segments against the average motion of all segments. The resulting pattern showed that, on the average, the midregion of the inferior wall began to contract 25 msec before the apex and the midregion of the anterior wall began contraction 18 msec before the apex. In 12 of 25 patients the interior and anterior walls both began to contrast before the apex. In only one of 25 patients did the apex begin to contract first. This sequences of contraction corresponds to the reported sequence of electrical activation for normal human left ventricles.

The serial electrophysiologic effects of bretylium were studied in 10 patients undergoing cardiac catheterization before giving the drug, at the end of bretylium tosylate-loading infusion (5 mg/kg/15 min), and after 1 h of intravenous drug maintenance (1.5 mg/min). Mean blood pressure increased during drug loading from 93.6 +/- 10.9 mm Hg to 121.1 +/- 16.2 mm Hg (p less than 0.01, t = 15 min) but returned toward control (100.9 +/- 18.7 mm Hg, p = NS) during drug maintenance (t = 75 min). Small changes in PR, QRS, QTc, AH, and HV intervals during spontaneous and paced rhythms were not significant. Comparison of the control electrophysiologic study with early and late postdrug studies showed no significant changes in corrected sinus node recovery times and in Wenckebach cycle lengths, but small decreases in refractory periods occurred. After drug loading, decreases in mean effective refractory periods of atrium, AV node, and right ventricle of 12, 2, and 16 ms, respectively, occurred (p = NS); during drug maintenance (t = 75 min), these refractory periods had decreased with respect to control by 21, 36, and 13 ms, respectively (p less than 0.05, 0.05, and 0.01). Functional refractory period of the AV node decreased at 75 min by 31 ms (p less than 0.01). The observed shortening of refractory periods contrasts with the direct effects of bretylium in isolated ventricular muscle and Purkinje fibers, which consist of prolongation of effective refractory periods and action potential duration. Thus, indirect (adrenergic) effects may be more important to overall clinical electrophysiologic actions not only acutely during loading but also during at least the first 60-90 min of maintenance therapy, which spans the expected time of initial clinical antifibrillatory response.

Endomyocardial biopsy is often used in the clinical evaluation of cardiac disease. Among 134 consecutive procedures (280 myocardial samples), 3 approaches were compared: right internal jugular (n = 69), femoral arterial (n = 30) and femoral venous (n = 35). The femoral venous approach is a new method with which a preformed guiding sheath is used to allow sampling of the apical right ventricular portion of the ventricular septum. Vascular access and myocardial sampling were successful in all femoral venous and left ventricular (LV) procedures; however, the internal jugular vein could not be located to allow biopsy in 12% of neck approaches (p less than 0.025). One case of pneumothorax occurred after an internal jugular approach. Chest pain occurred after 10% (3 patients) of the LV, 4% (3 patients) of internal jugular and 3% (1 patient) of femoral venous procedures. Hypotension associated with biopsy was noted after 3 internal jugular and 2 LV procedures. Pericardial effusion was observed in 3 patients after an LV procedure (p less than 0.01). In 1 of these patients tamponade developed. The femoral venous approach had the highest overall efficiency (successful biopsy, lack of adverse events, p less than 0.05). This approach may become the procedure of choice for routine endomyocardial biopsy because it allows reliable vascular access and myocardial sampling with a low incidence of adverse reactions.

The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 +/- 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 X 10(6) U/5 hr, n = 14 or 10(6) U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 +/- 1.0 hr after onset of pain in the intravenous and at 4.3 +/- 1.4 hr in the intracoronary drug group (p less than .001). Convalescent (day 10) radionuclide ejection fractions were 54 +/- 14% for the intravenous and 50 +/- 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p less than .08) vs 1.2% (NS). Semiquantitative regional wall motion indexes in the infarct zone showed significant and similar modest improvement from admission to day 10 in both groups (p less than .02). Accelerated enzyme-release kinetics were noted after both therapies. Times of peak enzyme levels for patients on intravenous and intracoronary drug were, respectively, 12.5 +/- 5.0 and 11.5 +/- 4.3 hr for creatine kinase MB isoenzyme and 31.7 +/- 11.8 and 28.1 +/- 12.7 hr for lactic dehydrogenase (LDH). Peak LDH-1 level was lower in patients receiving intravenous drug than in the historical control group (p less than .05). Electrocardiographically summed ST segments diminished rapidly after therapy in both groups; Q wave development was similar and overall R wave loss was equivalent and less extensive compared with in historical control subjects. Infarct pain requiring morphine was diminished similarly in both treatment groups. Incidence of early arrhythmias and heart failure also did not differ. Posttherapy ischemic events and early surgery tended to be more common in the intracoronary group and bleeding was more common in the intravenous group. Intravenous drug did not decrease early hospital mortality (intravenous drug = 5, historical control = 4, intracoronary drug = 1); the differences in this parameter among groups were not significant. At convalescent angiographic evaluation, anterograde perfusion was present in 73% of those receiving intravenous and 76% of those receiving intracoronary drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Destruction of central catecholaminergic nerve terminals and axons by the injection of 6-hydroxydopamine (6-OHDA) into a lateral cerebral ventricle lowered the resistance of rats to 4-h bilateral hindlimb ischaemia. Although treatment with 6-OHDA alters food intake and growth rate its effect on the resistance of rats to this injury could not be attributed to differences in the size of the limbs which were made ischaemic or in nutritional state. It was not seen after peripheral chemical sympathectomy produced by the intravenous injection of 6-OHDA. Pretreatment with intraventricular 6-OHDA affected the core temperature changes during and after the limb ischaemia and impaired the blood pressure response after removal of the tourniquets. The lesions in the hypothalamus associated with these changes were examined with fluorescence histochemistry and found to be severe and widespread. It was concluded that the catecholaminergic fibres innervating the hypothalamus and other parts of the brain concerned in homoeostasis play a beneficial role in the defence against injury.

The finding that naloxone reverses the arterial hypotension produced by bacterial endotoxin in the rat was confirmed and the effect of naloxone on the responses to another form of injury, limb ischaemia was studied. Naloxone had no effect on the fall in blood pressure and colon temperature or on behaviour and survival after bilateral hind-limb ischaemia. The ambient temperature threshold for the onset of shivering was depressed by limb ischaemia as in untreated rats. The increases in the plasma concentrations of glucose and corticosterone and the decrease in that of prolactin after limb ischaemia were unaltered by naloxone. In control rats naloxone reduced the ambient temperature threshold for the onset of shivering and the plasma prolactin concentration. It is concluded that the endogenous opioids do not play a very significant part in the responses to ischaemic limb trauma.

The ability to predict if abnormalities in regional wall motion are reversible would assist in selecting patients for aortocoronary bypass operation. This study shows that asynergic areas of the ventricle may be reversed by nitroglycerin. Thirty-four asynergic areas in 30 patients with coronary artery disease were studied before and after administration of nitroglycerin. Nineteen patients with previous infarction, diagnostic Q waves in their electrocardiogram, and akinetic areas in the left ventricle had no change in their akinetic areas after nitroglycerin administration. Nine of these patients did show increased motion in other hypokinetic areas of the myocardium. Five of 11 patients with no evidence of previous infarction showed a dramatic improvement in akinetic areas after nitroglycerin, while of the remaining 6, 5 showed mild improvement. This illustrates that recoverable asynergic areas may be recognized by nitroglycerin.

Recognition of pyrogen reactions in patients studied with multiple-use cardiac catheters led to recommendations regarding their cleaning and ultimately to the expensive practice of discarding catheters after a single use. Primarily because of cost considerations, our laboratory continued to clean and reuse catheters through 1981. This afforded an opportunity to assess the endemic rate of adverse reactions associated with this practice. We prospectively evaluated 341 patients who were studied with single-use or multiple-use catheters. The overall incidence of adverse reactions was: hypotension 27%, fever 3%, chills 3%, and all three 0.6%. There were no statistically significant increases in these reactions associated with the reuse of catheters. Bacterial infection did not appear responsible for these reactions, and it is possible that they were due to angiographic dye. We conclude that careful cleaning and reuse of catheters does not create an obvious increase in the risk of infection, and it appears to play a minor role, if any, in the development of other adverse reactions.

When good visualization of the left coronary artery and proximal branches is difficult, the longitudinally angulated projection has proved useful. An accessory for achieving this angulation with a conventional angiographic table and without sacrificing the advantages of video monitoring and the protection of lead vinyl shielding is described.

1. Shivering in the barbitone-anaesthetised cat exposed to a lowered ambient temperature was reduced by transient haemorrhagic or drug induced hypotension such that there was a positive correlation between mean arterial blood pressure and the intensity of shivering. 2. Shivering which had been reduced by haemorrhage could be restored by the reinfusion of blood, centripetal stimulation of a buffer nerve or by the intravenous administration of methoxamine. 3. The intensity of shivering was increased by the intravenous injection of methoxamine and by stimulation of a buffer nerve, although the latter response was attenuated by intact buffer nerves. 4. There was a marked variation in the importance of the different buffer nerves in maintaining shivering. 5. Shivering was abolished by deafferentation of the baroreceptors and although it could be restored by electrical stimulation of a buffer nerve methoxamine was then without effect. 6. A prolonged period (90-120 min) of hypotension (50-60 mm Hg) impaired the ability to shiver even after the hypovolaemia and hypotension had been corrected.

A system for three-dimensional reconstruction of dynamic (moving) vascular bed structures has been developed and is described. Input images are obtained from two-view (bi-plane or ECG correlated) X-ray angiograms. A target structure consisting of vessel branch points (nodes) and lines between the branch points is entered on the first of a sequence of images in one view. The movement of the nodes is indicated on subsequent images and on the images of the second view. The target is linearly warped according to the motion of the node points. Automatic edge detection (with subsequent operator correction) is used to detect centerlines and edges of vessels. Three-dimensional reconstruction is accomplished using a distance minimizing point matching technique. Finally, angle-corrected densitometric methods are used to refine the vessel cross section. Standard shaded surface display techniques are then used to display the moving arterial bed. Flow measurements are obtained by tracking the leading edge of the bolus down the three-dimensional arterial tree.

Noradrenaline (NA) fluorescence in the hypothalamus and brain stem of the rat has been examined during and up to 1.5 h after a 4-h period of bilateral hind-limb ischaemia. A decrease in the fluorescence of the NA terminals in the n. supraopticus and n. paraventricularis was seen during the second half of the period of limb ischaemia and became more marked 1.5 h after removal of the tourniquets. Changes in the preoptic-anterior hypothalamic (POAH) area and n. dorsomedialis occurred more slowly and depletion was best seen after the limb ischaemia. Measurements of the fluorescence with a microphotometer confirmed the changes seen in the POAH area, the n. supraopticus and the n. dorsomedialis 1.5 h after 4 h bilateral hind-limb ischaemia but suggested that the visual gradings of changes in the n. paraventricularis, which normally has a high NA content, could be unreliable. No changes were seen at any of the times studied in the ventral part of n. striae terminalis. The cells of origin of the affected terminals could not be identified since no changes were detected in the fluorescence of the cells in the NA nuclei of the brain stem. alpha-Methyl-p-typrosine, given at the start of the experiment to inhibit tyrosine hydroxylase, reduced the fluorescence of these cells but still no difference could be discerned between those in the control and injured rats. These results confirm the previous chemical findings of a fall in the NA concentration in the hypothalamus after injury with little change in that of brain stem. The results are discussed in relation to the effects of the injury on the homoeostatic functions of the hypothalamus.