Vasoactive hormones in endotoxin shock: A comparative study in cats and dogs

1 There is a growing concensus that myocardial performance in the early stages of experimental endotoxic and septic shock is relatively normal; however, recent reports have identified an intermediate phase of shock when myocardial dysfunction is clearly apparent. 2 The mechanism of dysfunction has become a subject of intense investigation. A current view is that altered myocardial responsiveness to circulating catecholamines may play an important role in the dysfunction observed after endotoxin administration. The present studies, in which an isolated working heart preparation of the dog was used, were designed to test this hypothesis. This particular experimental preparation was selected to provide an adequate interpretation of results; cardiac output, afterload, and concentrations of adrenaline reaching the coronary vascular bed were controlled in all experiments. Responses to infusions of adrenaline were recorded in the 'steady-state' condition. Control (non-shocked) heart responses to adrenaline were highly reproducible in terms of inotropic, chronotropic and coronary vascular behaviour. 3 Results from the study document myocardial dysfunction within 4-6 h following an LD70 endotoxin administration on the basis of increased left ventricular end diastolic pressure (LVEDP), decreased cardiac power and myocardial efficiency, and depressed negative and positive dP/dt parameters. 4 Findings suggest significantly altered responsiveness of the myocardium to infused adrenaline at rates of 1, 2, and 5 pg/min with concentrations between 10 and 1 ng/ml blood. LVEDP was elevated while calculated power and efficiency parameters remained significantly below control values during infusion of adrenaline in endotoxin-treated hearts. Depressions of responsiveness were interpreted to occur on the basis of failure to restore positive and negative dP/dt to normal values and depressed coronary blood flow responses during adrenaline administration. Increases in coronary flow were regularly less in experimental hearts than the controls. Heart rate responses to adrenaline in both failing and non-failing hearts were identical. 5 In conclusion, it is suggested that myocardial contractile and relaxation characteristics and coronary vascular responses to adrenaline infusion are depressed in endotoxin shock during the period of demonstrated myocardial dysfunction. No distinct causal relationships were observed between the ailtered myocardial responsiveness and pathogenesis of heart dysfunction since myocardial dysfunction and altered responsiveness to adrenaline were generally observed together. Myocardial oedema formation after endotoxin as previously reported by this laboratory may bear a relationship to the depressed negative dP/dt response to adrenaline.

Section: Introductionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Myocardial Failure With Altered Response to Adrenaline in Endotoxin Shock

Archer

Black

Hinshaw

1975

“…Production rates of angiotensin in the cat after haemorrhage are not known but in the dog, amounts up to 1-5 tug/min were formed (Regoli & Vane, 1966;Hodge, Lowe & Vane, 1966). After administration of endotoxin to cats, angiotensin production increased up to (62 ng/min)/kg and in one cat to more than (130 ng/min)/kg (Hall & Hodge, 1971). In our experiments, infusions of (100 ng/min)/kg caused a reduction in intestinal blood flow to 38% of control but hepatic blood volume decreased only to 80% of control.…”

Section: Discussionmentioning

confidence: 99%

Effects of infusions of catecholamines, angiotensin, vasopressin and histamine on hepatic blood volume in the anaesthetized cat

Greenway

Lautt

1972

Summary1. Hepatic volume was recorded by a plethysmographic technique in cats anaesthetized with pentobarbitone; the hepatic artery and portal vein remained intact. Dose-response curves were obtained for intravenous infusions of adrenaline, noradrenaline, angiotensin, vasopressin and histamine. 2. Adrenaline and noradrenaline decreased hepatic blood volume and did not differ significantly in potency. Up to 40% of the hepatic blood volume was expelled by doses within the range secreted by the adrenal medullae. 3. Isoprenaline, infused into the hepatic artery, had no significant effect on hepatic blood volume in doses which caused maximal vasodilatation of the hepatic arterial bed. Relaxation of hepatic capacitance vessels mediated by ,8-adrenoceptors did not occur.4. Angiotensin infusions in doses previously shown to cause intestinal and splenic vasoconstriction, decreased hepatic blood volume and on a molar or microgramme basis, angiotensin was the most potent of the agents tested. Doses within the probable physiological range of endogenous production decreased hepatic blood volume by up to 20%. The responses were not significantly different when the hepatic nerves were intact or sectioned. 5. Vasopressin infusions produced only small decreases in hepatic blood volume. Doses within the range secreted by the posterior pituitary which constrict the intestinal and splenic resistance vessels, did not decrease hepatic blood volume by more than 10%. 6. Histamine produced no change in hepatic blood volume in doses which readily produce outflow block in dogs. Either the specific hepatic venous smooth muscle involved in outflow block is absent in the cat or it has no histamine receptors. 7. After the rapid change in hepatic blood volume at the onset of the infusion, hepatic volume remained steady for the duration of each infusion. There was no evidence that these agents caused net transsinusoidal fluid movements.

“…These include histamine (Weil & Spink, 1957;Hinshaw, Jordan & Vick, 1961;Hinshaw, 1964), 5-hydroxytryptamine (5-HT) (Armin & Grant, 1957; Davies, McQuarrie & Meeker, 1959), angiotensin (Hall & Hodge, 1971), adrenaline and/or noradrenaline (Nykiel & Glaviano, 1961;H6kfelt, Bygdeman & Sekkenes, 1962;Hall & Hodge, 1971) and 'a cholinergic substance' (Vick, 1965). There is also early activation of the kallikrein-kinin system (Erdos & Miwa, 1968;Nies, Forsyth, Williams & Melmon, 1968;Al-Kaisi, Parratt, Siddiqui & Zeitlin, 1976).…”

Section: Introductionmentioning

confidence: 99%

THE POSSIBLE ROLES OF HISTAMINE, 5‐HYDROXYTRYPTAMINE AND PROSTAGLANDIN F_2α AS MEDIATORS OF THE ACUTE PULMONARY EFFECTS OF ENDOTOXIN

Parratt

Sturgess

1977

I In an attempt to investigate the possible role of released vasoactive substances in mediating the pulmonary pressor responses to E. coli endotoxin, cats were pretreated with histamine, 5-hydroxytryptamine (5-HT) or prostaglandin antagonists, with a histamine depleting agent (compound 48/80) or with an inhibitor of prostaglandin synthetase (sodium meclofenamate). 2 The administration of endotoxin (2 mg/kg) resulted in a rapidly developing pulmonary hypertension (pressure twice normal after 2-3 min), increases in right atrial and intratracheal pressures, systemic hypotension and bradycardia. These effects were unaffected by methysergide in a dose sufficient to prevent the effects of intravenously administered 5-HT. 3 Endotoxin responses were also unaffected by a combination of mepyramine and burimamide in doses sufficient to reduce markedly the effects of intravenously-administered histamine. In cats pretreated (chronically or acutely) with compound 48/80, endotoxin induced a transient pulmonary pressor response which was not maintained. 4 The pulmonary and systemic responses to endotoxin were prevented by the prior administration of the prostaglandin antagonist, polyphloretin phosphate and by pretreatment with the prostaglandin synthetase inhibitor, sodium meclofenamate. 5 It is concluded that a pulmonary vasoconstrictor prostaglandin is involved in the acute response to endotoxin in the cat.