Adrenergic influence on bile secretion—an experimental study in the cat

The influence on bile secretion of electrical stimulation of the splanchnic nerves and arterial infusion of adrenergic agonists was studied in anaesthetized cats. The bile salt secretion was supported by a continuous intravenous infusion of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced the volume outflow of bile from 0.71 to 0.44 ml h^-1 kg^-1 body wt and raised the bile acid concentration in bile, while the bile salt secretion rate was not affected. This response was reduced but not blocked by pretreatment with phentolamine, an α-adrenergic blocker, at a dose that prevented the blood pressure response. Infusion of noradrenaline, a mainly α-adrenergic agonist, into the hepatic artery mimicked the response. Infusion of isoprenaline, a β-adrenergic agonist, also reduced the volume outflow of bile from the liver. The biliary clearances of mannitol and polyethylene glycol 900, both of which are suggested to reflect canalicular events, were reduced by stimulation of the splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation of the α-adrenergic receptors reduces the bile acid-independent bile secretion. This reduction in bile flow induced by stimulation of the splanchnic nerves and infusion of noradrenaline is elicited mainly at the canalicular level.     

Effect of increased α-adrenergic activity on the blood pressure/cardiac output relationship in dogs

The relationship between mean aortic blood pressure (MAP) and cardiac output (CO) was examined in anaesthetized, open-chest dogs during variations in pre-load with and without α-adrenergic stimulation with phenylephrine. When phenylephrine increased MAP to 200 mmHg, CO fell greatly and could not be increased by volume expansion. Left ventricular ultrasonic measurements and pressure recordings showed that the Frank-Starling mechanism was maximally activated. During vena cava obstruction CO and MAP fell proportionally. At a lower infusion rate of phenylephrine, MAP increased to 160 mmHg without a great reduction of CO. As in control experiments without phenylephrine infusion, CO could be increased by dextran/saline infusion and lowered about 20% below control by vena cava obstruction with no significant change in MAP; by further caval obstruction CO and MAP fell in proportion. Phenylephrine did not alter the relationship between aortic baroreceptor activity and MAP. The same MAP/CO relationships were obtained before and after bilateral vagotomy and nephrectomy. Caval obstruction and pacing tachycardia resulted in similar MAP/CO relationships despite different effects on left ventricular end-diastolic pressure. Thus, phenylephrine infusion may raise MAP to 200 mmHg but no cardiac reserve is left. During reduction of CO by caval obstruction, peripheral vascular resistance remains constant despite varying baroreceptor activity. At the lower infusion rate of phenylephrine, raising MAP to 160 mmHg, peripheral vascular resistance is constant at low CO, but at high CO the vasoconstrictive effect of phenylephrine is counteracted by a vasodilatory mechanism which seems to be flow-dependent.     

Haemodynamic conditions for renal PGE2 and renin release during α- and β-adrenergic stimulation in dogs

Constriction of the renal artery and infusion of an α-adrenergic agonist induce autoregulated vasodilation and increase prostaglandin E₂ (PGE₂) and renin release. The enhancement of renin release during autoregulated vasodilation might be mediated by prostaglandins. To examine this hypothesis, experiments were performed in three groups of anaesthetized dogs. In six dogs constriction of the renal artery to a perfusion pressure below the range of autoregulation raised renin release from 2 ± 1 to 27 ± 6 μg AI.min^-1 and PGE₂ release from 1 ± 1 to 10 ± 2 pmol. min^-1. After administration of indomethacin (10 mg. kg^-1 b. wt), PGE₂ release was effectively blocked and constriction of the renal artery raised renin release only from 0.1 ± 0.1 to 6 ± 1 μg AI.min^-1. During subsequent continuous infusion of a β-adrenergic agonist, isoproterenol (0.2 μg. kg^-1.min^-1), constriction of the renal artery raised renin release from 0.1 ± 0.1 to 52 ± 11 μg AI.min^-1, although there was no rise in PGE₂ release. In six dogs, intrarenal infusion of phenylephrine, an α adrenergic agonist, increased PGE₂ and renin release before, but not after, indomethacin administration. In six other dogs, phenylephrine infused during isoproterenol infusion increased renin release equally before and after indomethacin administration. Thus the enhancing effect of constricting the renal artery or infusing an α-adrenergic agonist is not dependent upon prostaglandins. We propose that autoregulated dilation enhances renin release whether the stimulatory agent is a prostaglandin or a β-adrenergic agonist.     

Segmental distribution of vascular resistances during ureteral occlusion: The vasoconstrictive effects of angiotensin and CaCl2 differ from those of catecholamines and renal nerve stimulation

Examinations of renal autoregulation and renin release suggest that α-adrenergic agonists, in contrast to other vasoconstrictors, preferentially constrict the preglomerular arteries. To examine this hypothesis, experiments were performed in anesthetized dogs during ureteral occlusion. At a ureteral pressure (UP) of 100 mmHg the afferent arterioles are dilated and mechanical constriction of the renal artery does not alter intrarenal vascular resistances. Whereas angiotensin and CaCl₂ infused into the renal artery reduced renal blood flow (RBF) by 25–30% without reducing UP, renal nerve stimulation reduced RBF and UP in proportion. During angiotensin and catecholamine infusion, measurements of UP and intrarenal venous pressure permitted calculations of preglomerular, efferent vascular and intrarenal venous resistances. Until RBF was reduced by 25%, angiotensin raised both preglomerular and efferent vascular resistances, whereas norepinephrine and the α-adrenergic agonists, phenylephrine and methoxamine raised preglomerular more than efferent vascular resistance. When RBF was reduced by more than 25%, all vasoconstrictors showed a similar pattern with large increments both in preglomerular and efferent vascular resistances. Conclusions: Humoral and nervous stimulation of α-adrenergic receptors reduce glomerular capillary pressure by preferentially constricting the preglomerular arteries and may affect renal autoregulation and renin release by reducing the transmural pressure of the afferent arterioles.     

Mechanism of blood pressure elevation during angiotensin infusion

The mechanism of increased preload and its contribution to the rise in blood pressure during intravenous angiotensin infusion were studied in anesthetized dogs. In open-chest dogs angiotensin increased mean aortic blood pressure by 58±12 mmHg. Left ventricular end-diastolic dimension, measured as myocardial chord length (MCL) by ultrasonic technique, increased by 7±1 %. By inflating a balloon in the inferior vena cava, end-diastolic MCL was reduced to control value and the rise in mean aortic blood pressure was almost halved to 32±10 mmHg above control value. A similar preload effect was recorded in closed-chest dogs using end-diastolic left ventricular pressure as an estimate of left ventricular volume. During angiotensin infusion to the upper body only, end-diastolic MCL did not increase. When redistribution of the splanchnic blood volume was prevented, the effect of angiotensin on end-diastolic MCL was reduced to 1/3. Angiotensin reduced liver but not splenic dimension measured by ultrasonic technique. We conclude that about half of the rise in blood pressure during angiotensin infusion is due to increased end-diastolic volume caused by blood redistribution. About 2/3 of this increase in preload is due to redistribution from the splanchnic bed, mainly from the liver.     

Effect of crowding on corticosterone responses to central adrenergic stimulation

The social stress of crowding for 3, 7 and 14 days considerably reduced the increase in serum corticosterone elicited by intracerebroventricular administration of isoprenaline, a β-adrenergic agonist, on the 3rd and 7th days of crowding. The corticosterone response to clonidine, an α₂-adrenergic agonist, was significantly diminished only after 3 days of crowding and this reduction was paralleled by a significant decrease in hypothalamic histamine content. The stimulatory effect of phenylephrine, an α₂-adrenergic agonist, was not significantly changed by crowding stress. Social crowding stress caused almost total and persistent reduction in the hypothalamic-pituitary-adrenocortical (HPA) responsiveness to noradrenaline which stimulates the HPA axis via both α- and β-adrenergic receptors.

     

Cardiac performance: independent effects of inotropy and preload at high heart rate.

Linear relationships between stroke volume (SV) and heart rate (HR) were observed during right atrial pacing in open-chest dogs at control inotropy, during intravenous isoproterenol infusion and during blood volume expansion by saline infusion at HR exceeding 150 beats/min. The slope of these relationships remained constant during variations in inotropy, but rose during blood volume expansion. Myocardial chord lengths in the anterior left ventricular wall were continuously recored by ultrasonic technique to estimate left ventricular volume. When heart rate was increased, end-diastolic volume decreased more rapidly after than before blood volume expansion, explaining the increased slope of the SV/HR relationship. The end-diastolic volume and the SV/HR relationship were not influenced by changes in inotropy. After blood volume expansion by 57 +/- 13%, control end-diastolic volume was reestablished by increasing heart rate 84 +/- 20 beats/min. At identical end-diastolic volume, SV was equal at different HR. Thus, the effects on SV of changes in preload and inotropy are separable during right atrial pacing, and SV is independent of HR at constant preload and adrenergic stimulation.     

Relationship between PGE2 and renin release in dog kidneys Effects of afferent arteriolar dilation and adrenergic stimulation

To study the relationship between PGE₂ and renin release from the kidney, examinations were performed on anesthetized dogs during afferent arteriolar dilation. This condition is known to increase renin release and enhance the stimulatory effects on renin release of β-adrenergic agonists, such as isoproterenol. Afferent arteriolar dilation induced by constricting the renal artery or occluding the ureter increased PGE₂ and renin release before, but not after, indomethacin administration. Isoproterenol infusion during afferent arteriolar dilation increased renin release but not PGE₂ release both before and after indomethacin administration. Phenylephrine, an α-adrenergic agonist, which also induces afferent arteriolar dilation, increased PGE₂ and renin release at control blood pressure but not when the afferent arterioles already were dilated by ureteral occlusion. We conclude that afferent arteriolar dilation caused by renal arterial constriction, ureteral occlusion or infusion of phenylephrine increases prostaglandin synthesis which stimulates renin release. The effect of isoproterenol on renin release is independent of prostaglandin synthesis.     

Volume management in critically ill patients: New insights

In order to turn a fluid challenge into a significant increase in stroke volume and cardiac output, 2 conditions must be met: 1) fluid infusion has to significantly increase cardiac preload and 2) the increase in cardiac preload has to induce a significant increase in stroke volume. In other words, a patient can be nonresponder to a fluid challenge because preload does not increase during fluid infusion or/and because the heart (more precisely, at least 1 of the ventricles) is operating on the flat portion of the Frank-Starling curve. Volumetric markers of cardiac preload are therefore useful for checking whether cardiac preload effectively increases during fluid infusion. If this is not the case, giving more fluid, using a venoconstricting agent (to avoid venous pooling), or reducing the intrathoracic pressure (to facilitate the increase in intrathoracic blood volume) may be useful for achieving increased cardiac preload. Arterial pulse pressure variation is useful for determining whether stroke volume can/will increase when preload does increase. If this is not the case, only an inotropic drug can improve cardiac output. Therefore, the best option for determining the usefulness of, and monitoring fluid therapy in critically ill patients is the combination of information provided by the static indicators of cardiac preload and arterial pulse pressure variation.     

Contributions of blood drainage from the liver,spleen and intestines to cardiac effects of aortic occlusion in the dog

By occluding the descending thoracic aorta, blood transferred from the lower to the upper part of the body increases left ventricular end-diastolic volume and maintains stroke volume despite a rise in systolic left ventricular pressure (LVP) of about 60 mmHg. Seventy percent of the blood drained stems from the splanchnic circulation. To examine which splanchnic organs contribute to the cardiac effects, selective occlusions were performed during ultrasonic measurements of spleen and liver dimensions and left ventricular myocardial chord length (MCL) in atropinized, open-chest dogs. Drainage of 15±2 ml from the spleen accounted for 18±4% of the increase in end-diastolic MCL, whereas liver dimensions remained unaltered. Similar results were obtained during aortic occlusion at high inotropy (isoproterenol infusion). it was ascertained by occlusion of the coeliac and mesenteric arteries that about 50% of the cardiac response to aortic occlusion was due to drainage from the intestines and the aorta. Liver blood volume could be reduced by combined occlusion of the aorta and portal vein or coeliac and mesentenc arteries and was sensitive to changes in pressure in the inferior vena cava, but did not contribute to the cardiac response to aortic occlusion.     

Atrial natriuretic factor (ANF 103–126) enhances volume- and pressor-induced heart rate response in the conscious rat

The reduction in blood pressure due to ANF(103–126) fails to elicit reflex cardioacceleration in the conscious rat. To examine baroreflex sensitivity, the effect of ANF(103–126) on the heart period (HP) response to rapid central volume expansion and to alterations in mean arterial pressure (MAP) induced by bolus injections of phenylephrine and sodium nitroprusside was assessed. ANF(103–126) significantly augmented the bradycardic response induced by acute volume expansion from 426 ± 21 to 391 ± 23 beats min^-1 versus 421 ± 23 to 405 ± 24 without ANF(103–126). Baroreflex sensitivity was defined by the ratio of the change in heart period to the maximal change in mean arterial pressure. The dose of ANF(103–126) utilized did not affect basal heart rate or the magnitude of the mean arterial pressure response to phenylephrine but did significantly enhance the nitroprusside-induced decrease in mean arterial pressure. Baroreceptor sensitivity to phenylephrine was significantly increased by ANF(103–126): 0.997 ± 0.07 (ms mmHg^-1) during ANF(103–126) vs 0.613 ± 0.08 during vehicle. The total duration of the heart rate response to phenylephrine was also prolonged. In contrast, ANF(103–126) did not alter the baroreceptor sensitivity (1.45 ± 0.3 vs 1.43 ± 0.2 ms mmHg^-1) or duration of heart rate response to nitroprusside. In the conscious rat, ANF(103–126) modifies the heart rate response to changes in mean arterial pressure and acute central volume expansion. This action appears to be dependent on stimulation of cardiac vagal afferents.     

Circulating catecholamines and control of plasma renin activity in conscious dogs.

Uninephrectomized dogs were prepared with indwelling catheters in the aorta, inferior vena cava (IVC), and renal artery, and after recovery they were studied in the conscious state. Basal aortic epinephrine and norepinephrine concentrations were 57 +/- 11 and 101 +/- 18 pg/ml, respectively. Elevation of epinephrine concentration to over 2,000 pg/ml by IVC infusion resulted in a sustained 3.5-fold increase in plasma renin activity (PRA), with only a transient decrease in arterial blood pressure. The PRA response to epinephrine was completely blocked by l-propranolol; isoproterenol increased PRA more than did epinephrine. Increasing norepinephrine concentration to 1,600 pg/ml by IVC infusion resulted in only a 1.5-fold increase in PRA. Infusion of epinephrine or norepinephrine directly into the renal artery to achieve similar increments of renal arterial concentration did not increase PRA. Insulin injection or hemorrhage resulted in elevations of arterial epinephrine (but not norepinephrine) concentration greater than the concentrations achieved during IVC infusion in these studies. We conclude that circulating epinephrine in the physiologic range plays a role in the control of PRA by activation of an extrarenal beta-receptor.     

Angiotensin II infusion during β-adrenergic stimulation by isoproterenol. Effects on hepatic,splenic and cardiac blood volumes and on the magnitude and distribution of cardiac output in the dog

The cardiac and peripheral vascular adjustments to angiotensin II (0.1–0.2 μg kg^-1 min^-1 i.v.) during high β-adrenergic activity by a continuous isoproterenol infusion (0.2–0.3 μg kg^-1 min^-1 i.v.) were examined in anaesthetized, atropinized dogs. Hepatic, splenic and left ventricular (LV) volume changes were estimated by an ultrasonic-technique, and the blood flow distribution was measured by injecting radioactive microspheres and by electromagnetic flowmetry on the caval veins, the hepatic artery and the portal vein. During isoproterenol infusion, angiotensin II increased the systolic LV pressure by 45 ± 3 mmHg and the stroke volume by 17 ± 6 %. Concomitantly, the hepatic and splenic blood volumes declined by 29 ± 4 and 14 ± 6 ml, respectively, and the LV end-diastolic segment length increased by 3 ± 1 %. The flow through the inferior caval vein increased by 39 ± 9%, whereas the superior vena caval flow remained unchanged. The hepatic arterial flow more than doubled. Thus, at high inotropy by isoproterenol infusion, angiotensin II relocates blood from the liver and the spleen towards the heart. By activating the Frank-Starling mechanism, cardiac output is increased and conducted through the lower body, especially through the hepatic artery, because of the poor autoregulation of flow through this vessel.,     

Mechanisms of left ventricular filling during increased preload and inotropy

To examine the factors contributing to left ventricular filling, experiments were performed in anesthetized, open-chest dogs with intact or mechanically constricted mitral ostium. Stroke volume was raised either by increasing left ventricular end-diastolic volume (preload) by blood volume expansion or by infusing isoproterenol, a beta-adrenergic agonist. In all experimental settings, stroke volume rose in proportion (r greater than 0.9) to the pressure time product (PTP = integral of the diastolic atrio-ventricular (A-V) pressure difference). During saline infusion atrial distention and contraction increased atrial pressure more than ventricular pressure whereas diastolic filling time (DFT) was not lengthened. Peak mitral and peak aortic flow rose almost equally. During isoproterenol infusion at constant heart rate (atrial pacing), the increase in PTP was mainly caused by a longer DFT. When heart rate was allowed to rise, DFT was reduced and the A-V pressure difference increased because of a greater reduction in ventricular than in atrial pressure in early diastole. Thus, the A-V pressure difference is generated in different ways by raising preload and inotropy with and without changes in heart rate.     

Localization of Adrenergic Receptors in Guinea Pig Ileum and Rabbit Jejunum to Cholinergic Neurons and to Smooth Muscle Cells

The localization of adrenergic receptors mediating a relaxing action was investigated in innervated and denervated longituclinal muscle strips from guinea pig ileum and rabbit jejunum. Denervated preparations were contracted by drugs that had a direct effect on smooth muscle cells, such as acetylcholine and histamine, but not by stimuli acting on cholinergic neurons, such as electrical field stimulation or nicotine. After blockade of β-adrenoceptors, norepinephrine relaxed the innervated guinea pig ileum contracted by electrical field stimulation, by stimulating α-adrenoceptors. Norepinephrine in low concentrations did not relax denervated preparations contracted by agents acting directly on smooth muscle. In high concentrations, it relaxed denervated preparations by a nonadrenergic mechanism, resistant to α- and/or β-receptor blockade, but which was also activated by l-(3,4-dihydroxyphenyl) ethanol. Phenylephrine only had a weak agonistic effect on the electrically stimulated innervated preparation and did not relax the denervated one. The denervated rabbit intestine contracted by acetylcholine was relaxed by norepinephrine and phenylephrine by stimulation of α-adrenoceptors. In the innervated preparations both drugs were more effective in inhibiting contractions induced by electrical field stimulation or eserine than those induced by exogenous acetylcholine. Both the denervated guinea pig and rabbit intestine were relaxed by stimulation of β-adreno-ceptors. It is suggested that in the guinea pig ileum α-adrenoceptors mediating relaxation are located only in cholinergic neurons, whereas in rabbit jejunum they are located both in these neurons and in the smooth muscle cells. Beta-adrenoceptors are located in the smooth muscle cells of both organs.     

Cardiac effects of splanchnic and non-splanchnic blood volume redistribution during aortic occlusions in dogs

Translocation of blood from the lower body dilates the left ventricle during occlusion of the descending thoracic aorta and by increased activation of the Frank-Starling mechanism, stroke volume is maintained despite raised aortic blood pressure. The contributions from the splanchnic and non-splanchnic blood volumes to the left ventricular dilation were examined by ultrasonic measurements of myocardial chord length (MCL) in atropinized open-chest dogs. End-diastolic MCL rose by 2.5±0.9% during abdominal suprarenal aortic occlusion, draining blood from the non-splanchnic region, and by 7.4±1.7% during thoracic aortic occlusion draining blood from both splanchnic and non-splanchnic regions. Systolic left ventricular pressure rose by 16±3 mmHg and 76±12 mmHg, respectively. End-diastolic MCL rose by 6.0±1.2% during combined thoracic aortic and abdominal infrahepatic vena cava occlusion draining blood solely from the splanchnic region and further by 2.5±0.8% by blood drained from the non-splanchnic region after release of the vena cava occlusion. Similar results were obtained using a shunt permitting selective drainage first from the non-splanchnic region during thoracic aortic occlusion. Blood translocation from the non-splanchnic region maintains cardiac output during abdominal aortic occlusion. During occlusion of the thoracic aorta, drainage from the splanchnic region accounts for about 70% of the increase in end-diastolic MCL.     

Adrenergic influence on bile secretion--an experimental study in the cat

The influence on bile secretion of electrical stimulation of the splanchnic nerves and arterial infusion of adrenergic agonists was studied in anaesthetized cats. The bile salt secretion was supported by a continuous intravenous infusion of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced the volume outflow of bile from 0.71 to 0.44 ml h-1 kg-1 body wt and raised the bile acid concentration in bile, while the bile salt secretion rate was not affected. This response was reduced but not blocked by pretreatment with phentolamine, an alpha-adrenergic blocker, at a dose that prevented the blood pressure response. Infusion of noradrenaline, a mainly alpha-adrenergic agonist, into the hepatic artery mimicked the response. Infusion of isoprenaline, a beta-adrenergic agonist, also reduced the volume outflow of bile from the liver. The biliary clearances of mannitol and polyethylene glycol 900, both of which are suggested to reflect canalicular events, were reduced by stimulation of the splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation of the alpha-adrenergic receptors reduces the bile acid-independent bile secretion. This reduction in bile flow induced by stimulation of the splanchnic nerves and infusion of noradrenaline is elicited mainly at the canalicular level.     

Central hemodynamic effects of adrenaline with special reference to β2-adrenergic influence on heart rate and cardiac afterload in anesthetized cats

Central hemodynamic responses evoked by i. v.infusions of adrenaline and noradrenaline were studied in normovolemic anesthetized cats with intact adrenoceptors, after selective β₂-blockade (ICI 118,551), and after nonselective β-blockade (propranolol).The results demonstrated the presence of an important β₂-adrenergic component in the integrated response to ‘physiological’ doses of adrenaline contributing to increased cardiac output, decreased total peripheral resistance and virtually unchanged mean arterial blood pressure. Corresponding β₂-adrenergic effects of noradrenaline were small. The β₂-adrenergic effects of adrenaline on the heart seemed to be both direct and indirect. A moderate direct chronotropic response mediated by β₂-adrenoceptors apparently was present but there was no evidence of a direct β₂-adrenergic inotropic effect. An indirect, quite marked effect on the heart was accomplished by a β₂-adrenergic vasodilator interaction with the α-adrenergic vasoconstrictor influence on the systemic resistance vessels. This caused a net decrease in total peripheral resistance, thereby preventing an undue increase in cardiac afterload (arterial pressure) which seemed to be essential for evoking ‘optimal’ increases in cardiac output. It is suggested that such adrenaline evoked indirect, β₂-adrenergic improvement of cardiac performance is of functional importance in reflex sympatho-adrenal circulatory control.     

Effects of adrenergic blockade on the release of insulin,glucagon and somatostatin from the pancreas in response to splanchnic nerve stimulation in cats

The effects of α-,β- or α+β-adrenergic blockade on arterial plasma concentrations of insulin, glucagon and somatostatin in response to splanchnic nerve stimulation were studied in anesthetized cats. In control experiments splanchnic nerve stimulation caused a marked rise in plasma glucose and glucagon concentrations and a marked fall in insulin but somatostatin was unaffected. Pretreatment with phentolamine significantly increased basal plasma insulin concentration but the response pattern to splanchnic nerve stimulation was not altered. Propranolol attenuated both the glucose and insulin responses. Combined α-and β-blockade abolished the hyperglycemia and hypoinsulinemia induced by splanchnic nerve stimulation, whereas the rise in plasma glucagon was not affected. It is concluded that insulin release from the pancreas and glucose release from the liver is controlled by adrenergic mechanisms whereas pancreatic glucagon and somatostatin secretion is relatively insensitive to splanchnic nerve stimulation in cats.     

The effect of decreased intrathoracic pressure on ventricular function

SUMMARY  Large decreases in inspiratory intrathoracic pressure (ITP) occur during obstructive apnoeas. The cardiac effects of apnoea-associated decreased ITP come from the interaction of increased preload (venous return) on the right ventricle (RV) and increased afterload on the left ventricle (LV), and are modulated by the autonomic effects of shifts in blood volume and hypoxaemia. During obstructed breathing, venous return increases by as much as three-fold during inspiration even though mean flow may change little. This leads to a substantial inspiratory increase in RV end-diastolic and stroke volume. Because of ventricular interdependence, there is a decrease in LV diastolic compliance and corresponding decrease LV preload.
Sustained decreases in ITP (Müller manoeuvre) inhibit LV ejection, and hence increase LV afterload. However, breathing against an obstructed airway (repetitive short Müller manoeuvre) is not necessarily modelled by the sustained manoeuvre. Animal studies indicate that with airway obstruction, for the first beat or two of inspiration the primary effect on the LV is a reduction in stroke volume related to a decrease in preload, and afterload, if anything, decreases. In fact, afterload only increases during early expiration when stroke volume increases. When obstructive and central apnoeas are paired for duration and blood-gas alterations, there are increases in pulmonary blood volume with central apnoeas and in RV volume with obstructive apnoeas, consistent with the postulation that the primary effect of obstructive apnoeas is on venous return.
In conclusion, the putative role of decreased ITP in increasing LV afterload under conditions appropriate to OSA is not well supported by experimental studies. However, effects with very large swings in ITP as might be seen under the most extreme forms of OSA, and differences in timing of the swings between diastole and systole have yet to be investigated.