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Biomedical subjects

E Kirkman

Publications and source records attributed to E Kirkman.

34 records · Page 2Linked to original sources
PubMed1994

Ethanol augments the baroreflex-inhibitory effects of sciatic nerve stimulation in the anaesthetized dog.

Electrical stimulation of somatic afferent fibres in the sciatic nerve has been used as a model of injury in the anaesthetized dog. Stimulation of the sciatic nerve (during reflexly induced periods of apnoea to obviate any respiratory effects of sciatic stimulation) led to a simultaneous increase in arterial blood pressure and heart rate and a decrease in baroreflex sensitivity. Infusion of ethanol sufficient to produce clinically relevant plasma ethanol levels (100-200 mg %) had no consistent effects on baroreflex sensitivity, but enhanced the pressor response and significantly augmented the inhibitory effects of sciatic stimulation on the baroreflex. Since ethanol is commonly associated with injury in man, such changes in the response to 'injury' may modify the patients' cardiovascular response to the injury and complicate diagnosis.

Animals↗
PubMed1993

A comparison of the effects of skeletal muscle injury and somatic afferent nerve stimulation on the response to hemorrhage in anesthetized pigs.

The effect of skeletal muscle injury (SMI) on cardiovascular and O2 transport responses to hemorrhage (HS) were examined in anesthetized pigs. Bilateral hindlimb muscle was injured 75 minutes before HS was started at a rate of 0.75 mL/min.kg until a total of 30 mL/kg (40% estimated total blood volume) had been removed. The reductions in cardiac index (CI), left ventricular stroke work, and oxygen delivery (Do2) and the increase in plasma lactate concentration following HS were exacerbated by SMI such that although oxygen consumption was maintained after HS it fell after SMI + HS. The deleterious effect of SMI on the response to HS was greater than that recorded previously following somatic brachial nerve stimulation (BNS). Thus, in order to achieve a given reduction in CI and Do2 or a rise in Shock Index (heart rate divided by systolic blood pressure) to approximately 3, a blood loss of 40% was needed after HS; this was reduced to 36% by the addition of BNS, whereas a loss of only 29% was needed when SMI was introduced. The mechanism of the deleterious effect of SMI is unclear although a change in the distribution of regional blood flow and a rise in the critical oxygen delivery may be implicated.

Anesthesia↗
PubMed1993

Intravenous cefazolin in penetrating eye injuries. Treatment of experimental posttraumatic endophthalmitis.

The use of intravenous antibiotics as prophylaxis in penetrating eye injuries is strictly empiric and not based on scientific data supporting their use. To determine the efficacy of prophylactic intravenous cefazolin in penetrating eye injuries, a rabbit model of posttraumatic endophthalmitis was developed. Forty rabbits received penetrating eye injuries followed immediately by an intravitreal inoculum of live Staphylococcus epidermidis. The rabbits then were randomly divided into four groups: group 1 received three doses of intravenous cefazolin; group 2 received six doses, and group 3 received nine doses; group 4 received no treatment and served as controls. All control rabbits developed 4+ vitreitis; rabbits receiving three doses of the antibiotic developed 2+ vitreitis, and those receiving six or nine doses of cefazolin showed no vitreous inflammation (P < or = 0.0001). Histologic examination of control eyes showed an exuberant reaction with formation of retrolental membranes, vitreous abscess, and retinal detachment. Eyes treated with nine doses of cefazolin were devoid of inflammatory cells. These findings suggest that intravenous cefazolin is effective in preventing the development of posttraumatic endophthalmitis in a rabbit model.

Animals↗
PubMed1993

The neuropeptide CRF is involved in the modulation of the baroreflex during hindlimb ischaemia in the anaesthetized rat.

1. The effects of bilateral hindlimb ischaemia (BHLI), and of administration of the neuropeptide corticotrophin-releasing factor (CRF), were tested on cardiovascular variables in propofol-anaesthetized Sprague-Dawley rats. In addition, the effects of antagonizing endogenous CRF on the cardiovascular response to BHLI was investigated. 2. BHLI produced significant increases in mean arterial pressure and heart rate. Baroreflex sensitivity was reduced in all animals tested both 10 and 30 min after the induction of ischemia and this was accompanied by changes which are consistent with an underlying baroreflex resetting. 3. Intracerebroventricular (I.C.V.) administration of CRF (1.5 nmol) produced significant increases in heart rate but not mean arterial pressure. CRF also produced significant reductions in baroreflex sensitivity 10 and 30 min after administration, but there was no consistent evidence of baroreflex resetting. These effects of CRF could be prevented by pretreatment with the synthetic CRF antagonist, alpha-helical CRF(9-41) (alpha hCRF, 6.5 nmol, I.C.V.), which itself had no effect on these cardiovascular variables. 4. Pretreatment with alpha hCRF (6.5 nmol, I.C.V.) prevented the reduction in baroreflex sensitivity observed 10 min after the induction of BHLI, but had no consistent effect on the pressor or tachycardiac responses to BHLI and allowed a clear expression of BHLI-induced baroreflex resetting. alpha-Helical CRF(9-41) had no effect on the reduction in baroreflex sensitivity after 30 min of BHLI. 5. We conclude that corticotrophin-releasing factor mediates, at least in part, the early reduction in baroreflex sensitivity observed during hindlimb ischaemia in the rat.

Anesthesia↗
PubMed1993

Regional cerebral blood flow and carbon dioxide reactivity after noncerebral injury in the rat.

A loss of cerebral autoregulation and vascular reactivity to CO2 has been reported after a direct head injury; however, little has been published concerning the effect of CO2 after peripheral injury. In the present study, the effects of extracranial injury (bilateral hindlimb ischaemia followed by reperfusion) were studied on regional cerebral blood flow in the hypothalamus and cortex and on the changes in these blood flows induced by altering PaCO2 in the conscious rat. After release of the tourniquets, when fluid was being lost from the circulation into the postischaemic hindlimbs, there was a decrease in regional cerebral blood flow (rCBF). Administration of CO2 at this time markedly increased rCBF. There was no evidence that cerebrovascular responsiveness to hypercapnia was impaired after peripheral injury in the rat.

Animals↗
PubMed1992

Resuscitation fluids and oxygen transport in haemorrhagic shock.

This study examined the cardiovascular and oxygen transport/consumption relationships in haemorrhagic shock and resuscitation using Human Albumin and Gelatin solutions in a porcine haemorrhagic shock model. Immature pigs (17-25 kg) were anaesthetised and ventilated with nitrous oxide, oxygen and isoflurane. Aortic pressure monitoring and monitoring of pulmonary pressures and cardiac output via a Swan-Ganz catheter were instituted. A controlled haemorrhage of 40% of blood volume at 1% blood volume per minute was followed 30 minutes later by resuscitation with 60% of blood volume of 4.5% Human Albumin (Immuno) or 4% Modified Fluid Gelatin (Gelofusine). Haemorrhage caused marked decreases in (CI), mean arterial pressure and oxygen delivery (DO2). Oxygen consumption (V02) remained unchanged. Resuscitation with Albumin and Gelatin raised CI to values 60% to 70% above control though only Albumin restored DO2. Deterioration was more rapid in the Gelatin group due to the estimated half a life of 3 hours in this model. Oxygen extraction was 10% higher in the Gelatin group 2 hours after resuscitation. The role of oxygen radicals in haemorrhagic shock is discussed.

Albumins↗
PubMed1992

Lower limb ischaemia and reperfusion alters gut permeability.

The gut may be important in the aetiology of multiple organ failure (MOF) by amplifying of the inflammatory response to trauma. We investigated the effects of the reperfusion of ischaemic lower limbs on gut permeability. Male Wistar rats (n = 30) were randomised to (group 1) controls; (group 2) 3 h bilateral hind-limb ischaemia alone; or 3 h ischaemia followed by (group 3) 15 min reperfusion or (group 4) 2 h reperfusion. Gut permeability and plasma endotoxin were measured prior to tourniquet application, immediately before tourniquet release, and following reperfusion. To evaluate the effect of the hypotension that follows tourniquet release, (group 5) sodium nitroprusside was infused in further controls to maintain mean arterial pressure (MAP) at 75 mmHg for 2 h. Horseradish peroxidase was instilled into the isolated ileo-caecal loop 15 min before the animals were killed to measure permeability of horseradish peroxidase through mucosal intercellular tight junctions by electron microscopy. Mean arterial pressure increased from 105 +/- 5 mmHg to 136 +/- 4 mmHg on tourniquet application and fell to 79 +/- 7 mmHg following reperfusion (p less than 0.05). In group 1 (controls), group 2 (ischaemia alone animals) and group 5 (ischaemia and nitroprusside) one animal out of six demonstrated permeability to horseradish peroxidase. Following reperfusion, horseradish peroxidase permeability had not developed by 15 min (group 3) but was present in all animals by 2h (group 4) (p = 0.015 Fisher's exact test). Plasma endotoxin increased from 21.8 +/- 2.0 pg ml-1 to 30.7 +/- 2.6 pg ml-1 following 2 h reperfusion (p less than 0.05 Scheffe F-test).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effect of nociceptive stimulation on the changes in hemodynamics and oxygen transport induced by hemorrhage in anesthetized pigs.

The effects of somatic nociceptive afferent stimulation on aspects of cardiac function and oxygen transport were examined in a model of hemorrhage in anesthetized pigs. The brachial nerves were stimulated (BNS) alternately to obtain a rise in heart rate of 18% and in mean arterial pressure of 17%. This stimulation was started 75 minutes before the start of hemorrhage and maintained throughout and after the withdrawal of blood. The animals were bled at a rate of 0.75 ml/min.kg until a total of 30 ml/kg had been removed. At the end of hemorrhage the reductions in cardiac index (CI), stroke volume (SV), and left ventricular stroke work (LVSW) were greater in the BNS group compared with controls. The nociceptive stimulation also elicited greater reductions in oxygen delivery (DO2I) and oxygen consumption (VO2) and a greater rise in the arterial plasma lactate concentration. Thus it seems that nociceptive stimulation exacerbates the changes in systemic oxygen transport and cardiac function induced by hemorrhage.

Animals↗
PubMed1990

The involvement of the midbrain periaqueductal grey in the cardiovascular response to injury in the conscious and anaesthetized rat.

Cell bodies within the periaqueductal grey (PAG) of the midbrain of the propofol-anaesthetized rat were stimulated using the excitotoxin kainic acid. This resulted in a rise in arterial blood pressure and a tachycardia, together with a reduction in the sensitivity and a rightward resetting of the baroreflex. These changes mimicked the cardiovascular effect of bilateral hindlimb ischaemia in the rat. Further experiments in conscious rats indicated that electrolytic lesions in the PAG prevented the reduction in baroreflex sensitivity induced by limb ischaemia, but did not abolish the rightward resetting of the reflex or the pressor response and tachycardia when compared with sham-lesioned controls. It is postulated that the PAG, a site of importance both in the integration of the defence reaction and the processing of afferent nociceptive information, may form part of a pathway involved in the reduction of the sensitivity of the baroreflex following injury. This pathway is suggested to be separate from a second, as yet undefined, pathway mediating the baroreflex resetting and pressor responses associated with injury.

Anesthesia, Local↗
PubMed1989

Attenuation of the acute cardiovascular responses to haemorrhage by tissue injury in the conscious rat.

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.

Animals↗
PubMed1989

Differential modulation by pulmonary stretch afferents of some reflex cardioinhibitory responses in the cat.

1. Cats were anaesthetized with a mixture of chloralose and urethane, and were artificially ventilated, the thorax being opened via a medial sternotomy. 2. Various cardiovascular receptors were stimulated during reflex inhibition of the central inspiratory neurones produced by electrical stimulation of both superior laryngeal nerves simultaneously, while the afferent input from the lungs was held constant by temporarily interrupting artificial respiration, the lungs being held static in their expiratory position. 3. Reflex cardioinhibitory responses were elicited by stimulation of (a) the carotid body chemoreceptors by intracarotid injections of cyanide; (b) the arterial baroreflex by controlled elevations of the blood pressure; (c) the carotid sinus baroreceptors by raising the pressure in isolated perfused carotid sinus preparations; (d) cardiac receptors by left atrial injections of veratridine, and (e) pulmonary C fibres (including J receptors) by right atrial injections of phenyl biguanide. 4. The effects of single inflations of the lungs on these reflex cardioinhibitory responses were studied and compared with the effects of the various inputs alone. 5. Stepwise increases in lung volume, while having no consistent effect on arterial blood pressure, progressively diminished the arterial chemoreceptor-induced bradycardia to a value of about 7% of the control response without lung inflation. The pulmonary afferents were less effective on reflex responses from other inputs, the corresponding values being: arterial baroreflex, 66%; carotid baroreceptors, 66%, and cardiac receptors, 70%. These effects of lung inflation were abolished by selective denervation of the lungs. 6. In contrast, the size of the bradycardia evoked by pulmonary C fibre stimulation was, on average, unaffected by inflation of the lungs. In some tests the response was actually increased. 7. The differential modulation by lung inflation of these reflex cardioinhibitory responses were the same after upper thoracic sympathectomy indicating that pulmonary afferents and cardiac efferents involved fibres in the vagus nerves. 8. The possible central mechanisms responsible for the differential modulation by lung inflation of cardioinhibitory reflexes are discussed.

Animals↗
PubMed1988

Cardiovascular responses to stimulation of pulmonary C fibres in the cat: their modulation by changes in respiration.

1. In cats anaesthetized with a mixture of chloralose and urethane, stimulation of pulmonary C fibres by right atrial injections of phenylbiguanide caused, after a latency of about 3 s, a reduction in pulmonary ventilation or apnoea, bradycardia and systemic hypotension, confirming previous work. 2. A decrease in femoral artery perfusion pressure also occurred under conditions in which the hindlimb was vascularly isolated, the blood flow was maintained constant and the inferior vena caval pressure did not change. This indicates a reduction in vascular resistance due to vasodilatation. The response was unaffected by atropine and propranolol, but was reduced or abolished by guanethidine, hexamethonium and denervation of the limb, indicating that it is due to a reduction in activity in sympathetic vasoconstrictor fibres. 3. Similar cardiovascular responses were observed when the arterial blood pressure was maintained constant, and also in artificially ventilated animals. 4. Evidence is presented that the receptors responsible for the respiratory and cardiovascular responses to right atrial injections of phenylbiguanide lie in the pulmonary vascular bed. 5. When the pulmonary C fibres were excited during a period of apnoea which was induced reflexly by electrical stimulation of the central end of a superior laryngeal nerve, there were no consistent differences in the size of the cardiac or vascular responses compared to the control responses in the absence of the laryngeal input. This result occurred irrespective of the size of the control ventilatory response to phenylbiguanide. 6. By contrast in the same experiments, the cardio-inhibitory and vasoconstrictor responses to excitation of the carotid body chemoreceptors were invariably potentiated by electrical stimulation of a superior laryngeal nerve, as found previously. 7. The possible central mechanisms responsible for the differential modulation of pulmonary C fibre and carotid chemoreceptor reflexes by respiration are discussed.

Animals↗
PubMed1988

Cardiovascular responses to stimulation of cardiac receptors in the cat and their modification by changes in respiration.

1. In cats anaesthetized with a mixture of chloralose and urethane, stimulation of cardiac receptors by left atrial injections of veratridine had little or no effect on pulmonary ventilation but caused bradycardia, systemic hypotension and hindlimb vasodilation with a latency of 3.3 s. 2. The hindlimb vasodilatation was due largely, if not entirely, to a reduction in sympathetic vasoconstrictor activity. 3. Similar cardiovascular responses occurred when the arterial blood pressure was maintained constant and also in artificially ventilated animals. 4. When the cardiac receptors were excited during a period of apnoea which was induced reflexly by electrical stimulation of the central cut end of a superior laryngeal nerve, the cardio-inhibitory response to left atrial injections of veratridine was enhanced but the size of the vasodilator response was unaffected. 5. In contrast, the cardiovascular effects of stimulation of the carotid body chemoreceptors, bradycardia and hindlimb vasoconstriction were enhanced by the laryngeal input. 6. The possible central mechanism responsible for the differential modulation of cardiac receptor and carotid chemoreceptor reflexes by respiration are discussed.

Animals↗
PubMed1983

Resetting of the baroreceptors by atenolol in the anaesthetized cat.

In anaesthetized cats, atenolol (3 mg X kg-1 i.v.) produced an immediate reduction in blood pressure, heart rate and aortic nerve discharge. However, 30 min and 60 min after atenolol there was a shift to the left of the curve relating aortic nerve discharge to mean arterial blood pressure indicating a delayed resetting of the baroreceptors. There was no evidence that atenolol altered the sensitivity of the baroreceptors.

Anesthesia, General↗