Effect of artificial respiratory volume on the cardiovascular responses to an α₁‐ and an α₂‐adrenoceptor agonist in the air‐ventilated pithed rat

Abstract

1 The effect of varying artificial respiratory volume (at a fixed rate of 54 min-) on cardiac output, its distribution and tissue blood flows were determined with tracer microspheres in control pithed rats or during pressor responses to either the a1-adrenoceptor agonist phenylephrine or the a2-agonist xylazine. Phenylephrine was investigated in the presence of propranolol (3 mg kg 1). The rats were pithed under halothane anaesthesia. 2 A respiratory volume of 15 ml kg-produced modest hypercapnia (Paco2 = 47 mmHg), hypoxia (Pao2 = 60 mmHg) and acidosis (pH = 7.35) relative to control animals respired at 20 ml kg1 (Paco2 = 32 mmHg; Pao2 = 77 mmHg; pH = 7.47). In rats respired at 15 ml kg 1, total peripheral resistance was lower, and cardiac output greater (due to increased stroke volume), than in the controls. Lowering respiratory volume reduced distribution of cardiac output to the kidneys, increased it to the large intestine and also increased blood flow through the gastrointestinal tract, skin and spleen. A respiratory volume of 30 ml kg-1 gave mild hypocapnia (Paco2 = 19 mmHg), hyperoxia (Pao2 = 101 mmHg) and alkalosis (pH = 7.59) compared to 20 ml kg'-but had no effect on cardiac output distribution or organ blood flow although heart rate was 29% greater at 30 ml kg-'. 3 Xylazine (500 pg bolus followed by lOOI gmin1 infusion) at all three respiratory volumes gave well-sustained mean pressor responses of 62-64 mmHg by increasing both total peripheral resistance and cardiac output (resulting from increased stroke volume). It increased the proportion of cardiac output passing to the liver, reduced that going to the spleen and gastrointestinal tract and increased cardiac, renal and hepatosplanchnic blood flows. 4 The secondary, relatively sustained, pressor effect of phenylephrine (5 pg bolus followed by 0.4 pg min1 infusion, i.v.) varied at the 3 respiratory volumes with mean values from 32 to 53 mmHg. This response was due to both increased total peripheral resistance and cardiac output (resulting from greater stroke volumes and/or heart rates). Phenylephrine increased the proportion of cardiac output passing to the gastrointestinal tract, heart, kidneys and hepatosplanchnic bed and increased cardiac, hepatosplanchnic, renal and gastrointestinal blood flows. 5 Respiratory volume had no effect on the cardiovascular effects of xylazine. However, respiratory volume modified the effects of phenylephrine on heart rate and changed the relative contributions of stroke volume and heart rate to the increased cardiac output. It also influenced the effects of phenylephrine on cardiac output distribution to the liver, epididimides and hepatosplanchnic bed and on blood flow through skeletal muscle and the large intestine. 6 Changes in respiratory volume of air ventilated pithed rats thus influence cardiac output, its distribution and regional blood flows. Such changes can also differently influence the responses of various vascular beds to phenylephrine whilst having no effect on their responses to xylazine.

Cardiovascular responses to verapamil and nifedipine in hypoventilated and hyperventilated rats

“…Hyperventilation or hypoventilation was found to cause significant increases or decreases, respectively, in the blood pressure and pulse rate. This phenomenon is not at variance with the effects of blood gases, pH or ventilator stroke volumes on cardiovascular parameters found by others (Nahas & Cavert, 1957, Grant et al, 1985Phillips et al, 1985;MacLean & Hiley, 1988). The changes in pulse rate may result from a reflex increase or decrease in activities of the vagus nerve, the pulmonary stretch mechanoreceptors or cardio-inhibitory centre, or a combination of several of these factors (Daly & Scott, 1958;Evans & Evans, 1968).…”

“…Dai & Wong (1985) found that in urethane-anaesthetized rats, the effects of adrenaline on blood pressure, and of adrenaline or acetylcholine on pulse rate, were significantly reduced during hypoventilation which induced hypoxaemia, hypercapnia and acidosis. MacLean & Hiley (1988) also revealed that changes in artificial respiratory volume and the attendant blood gas and pH changes caused variations in cardiovascular responses to phenylephrine in the pithed rat.…”

Antiarrhythmic properties of tedisamil (KC8857), a putative transient outward K+ current blocker

“…When required, pentobarbitone (45mg kg-') was used for anaesthesia and animals artificially ventilated with°2 at a stroke volume of 10mlkg-1, 60min-'; a regimen which has been found to keep blood gases at normal levels (Maclean & Hiley, 1988). Body temperature was maintained at 37.0 + 0.50C by means of a thermocouple linked to a heating lamp.…”

Pressor effects of the α2‐adrenoceptor agonist B‐HT 933 in anaesthetized and haemorrhagic rats: comparison with the haemodynamic effects of amidephrine

“…This may be explained by very slow capillary blood flow, caused by hypotension, arteriolar vasoconstriction and open capillaries (Hardaway, 1985), leading to reduced oxygen delivery and an increase in anaerobic metabolism; the resulting lactic acidaemia causing hypocapnia as CO2 is blown off. Pressor responses to phenylephrine and xylazine, respectively selective agonists at a1-and x2-adrenoceptors, are not affected by changes in blood gases and pH within the range observed after haemorrhage here (MacLean & Hiley, 1988a). Therefore it is unlikely that such changes caused the altered pressor responses to amidephrine and B-HT 933.…”