Influence of naloxone on the total capacitance vasculature of the dog.

The opiate antagonist, naloxone, which is associated with prolonged survival in animal models of shock, has been demonstrated to increase arterial pressure and cardiac output. It is possible that the increase in cardiac output is due to a decrease in volume in the total capacitance vasculature and a subsequent increase in venous return. Because the influence of naloxone on the capacitance vasculature is unknown, the present study was undertaken to determine the influence of naloxone on intravascular volume in the total capacitance circulation. In 31 anesthetized dogs, blood from the vena cavae was drained into an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in total intravascular volume could be measured as reciprocal changes in reservoir volume. In five animals, naloxone infusion (2 mg/ml X min for 20 min) was associated with a decrease in total capacitance volume of 121 +/- 30 ml (P less than 0.05). To determine regional volume effects, naloxone was infused in 11 animals in which the splanchnic and extrasplanchnic vasculatures were separately perfused and drained: total and splanchnic volume decreased 64 +/- 13 ml (P less than 0.05) and 126 +/- 17 ml (P less than 0.0001), respectively, and extrasplanchnic volume increased 62 +/- 13 ml (P less than 0.001). After ganglionic blockade with mecamylamine (n = 3), total volume decreased 89 +/- 16 ml (P less than 0.05), splanchnic volume did not change, and extrasplanchnic volume decreased 91 +/- 32 ml (P less than 0.05). In another five animals, naloxone was infused during diversion of the splanchnic venous outflow to a nonrecirculating extracorporeal reservoir: total volume decreased 122 +/- 33 ml (P less than 0.05), splanchnic volume did not change, and extrasplanchnic volume decreased 101 +/- 16 ml (P less than 0.01). When the splanchnic venous effluent was reinfused without naloxone administration (n = 4), total volume decreased 43 +/- 5 ml (P less than 0.05), splanchnic volume decreased 113 +/- 14 ml (P less than 0.05), and extrasplanchnic volume increased 68 +/- 10 ml (P less than 0.05). Thus, naloxone is associated with a decrease in total capacitance volume, which is due entirely to a decrease in splanchnic volume. The splanchnic volume decrement would appear to be mediated through neurogenic and hormonal influences. In an animal not on bypass, it would be expected that naloxone would be associated with a decrease in total capacitance volume and subsequent increases in venous return and cardiac output.

Reflex influence of selective coronary artery occlusion on the total capacitance vasculature in the dog.

While the reflex influence of selective coronary arterial occlusion on the resistance vasculature has been well delineated, the reflex influence of coronary occlusion on the total capacitance vasculature has not been examined. Thus, selective coronary occlusions were performed in 65 anesthetized dogs. Blood was drained from the vena cavae and returned to the right atrium at a constant rate so that changes in total intravascular volume could be recorded as reciprocal changes in extracorporeal reservoir volume. In 10 animals, 2.5 min of left anterior descending occlusion was associated with only an insignificant total volume increase of 6 +/- 4 ml (SEM), whereas 2.5 min of left circumflex occlusion was associated with a 27 +/- 4 ml (P less than 0.001) increase in volume, which was significantly attenuated (P less than 0.001) to only a 7 +/- 3 ml increase after cervical vagectomy. Epicardial lidocaine in four animals reduced the volume increment associated with circumflex occlusion from 30 +/- 3 to 11 +/- 4 ml (P less than 0.025). The volume increase was attenuated from 45 +/- 6 to 24 +/- 5 ml with propranolol administration (P less than 0.001) (seven animals) and from 26 +/- 5 to 17 +/- 6 ml with atropine (P less than 0.025) (eight animals), but was not attenuated with phenoxybenzamine (28 +/- 7 ml before and 25 +/- 2 ml after phenoxybenzamine) (five animals). Double blockade with propranolol and atropine reduced the volume increase to 3 +/- 2 ml (NS) in four of these animals. In order to compare the influences of selective beta-1 adrenergic blockade and combined beta-1 and beta-2 blockade, volume responses were assessed before and after administration of metoprolol or propranolol in doses that produced the same amount of beta-1 blockade (15 animals). The volume increase associated with circumflex occlusion was not attenuated after beta-1 blockade (20 +/- 4 ml before and 18 +/- 5 ml after metoprolol) (eight animals) but was attenuated from 30 +/- 5 to 14 +/- 5 ml after propranolol (P less than 0.05) (seven animals). To examine further the efferent limb of the observed reflex, circumflex occlusions were performed before and after either vagectomy at the level of the diaphragm or section of the sympathetic splanchnic nerves in 12 animals. The volume increment was significantly attenuated after either procedure. In four animals undergoing prior arterial baroreceptor denervation, volume still increased 30 +/- 6 ml (P less than 0.001) with circumflex occlusion. Thus, inferior myocardial ischemia is associated with an autonomic reflex that acts to increase total intravascular volume. The afferent limb is mediated through the vagi, and the efferent limb, throug

Effect of ouabain on total vascular capacity in the dog.

Whereas the cardiac effects of digitalis glycosides have been extensively studied, less is known of the extracardiac effects of the drug, in particular the effects on vascular capacity. We investigated the effects of parenteral ouabain on vascular capacity in the dog with particular emphasis on transhepatic resistance and its interaction with splanchnic and total intravascular capacity. We studied 49 dogs on total cardiopulmonary bypass in which the splanchnic and extrasplanchnic circulations could be separately perfused and drained, and the portal vein could be vented to systemic venous pressure. The results indicate: (a) ouabain produces a net central displacement of blood at 30 min after administration of 150 +/- 70 ml (SEM), (b) this displacement occurs despite a substantial increase in transhepatic resistance, although the early rise in transhepatic resistance may delay the net displacement of blood, and (c) the decrease of overall vascular capacity is due to an effect of ouabain on the capacitance vessels of both the splanchnic and extrasplanchnic circulations. The peripheral vascular capacity effects of ouabain may therefore contribute to overall cardiac performance.

Endotoxemia alters splanchnic capacitance.

The splanchnic circulation constitutes a major portion of the total capacitance vasculature and may affect venous return and subsequently cardiac output during low output states. This study assessed the effects of rapid (10 microg/kg over 5 min) and slow (10 microg/kg over 60 min) induction of endotoxin (Escherichia coli) shock on splanchnic blood volume in 8 farm swine. Blood volume was measured by using Tc99m-labeled erythrocytes and radionuclide imaging. Baseline arterial pressure (MAP), central venous pressure (CVP), and liver, splenic, mesenteric and total splanchnic volumes were stable during the 30-min baseline. Approximately 30 min after the rapid endotoxin infusion, splenic volume decreased by 45%, whereas liver volume increased by 40% and MAP decreased by 60% (P < 0.01). The reduction in splenic volume occurred within 10 min of the endotoxin infusion, whereas liver volume changes occurred after MAP reduction. The slow endotoxin infusion also reduced splenic volume by approximately 50% (P = 0.05), whereas MAP declined by 30% (P < 0.05). However, the slow endotoxin infusion lowered liver volume (P < 0.05). Mesenteric volume was unaffected by the fast or slow endotoxin infusion. Total splanchnic volume was unaffected by the fast infusion but decreased by 37% in the slow infusion group (P < 0.05). In summary, E. coli endotoxin reduces splenic blood volume and increases liver blood volume after acute hypotension ensues. Endotoxin does not increase total splanchnic blood volume and may actually decrease total splanchnic volume in the absence of circulatory collapse. This endotoxin shock model is not associated with blood volume pooling in the splanchnic capacitance circulation.

Influence of nitroglycerin on splanchnic capacity and splanchnic capacity-cardiac output relationship.

It has been postulated, but not tested directly, that nitroglycerin's venodilatory effects attenuate cardiac output. Thus, the present study examined the importance of changes in splanchnic capacity, as assessed by scintigraphy, in the regulation of cardiac output during nitroglycerin administration in 16 anesthetized pigs under conditions of carotid sinus denervation and cervical vagotomy. With nitroglycerin administration (0.5 mg/min i.v.) for 5 min, systemic arterial pressure decreased from 115 +/- 7 to 95 +/- 7 mmHg (P < 0.0001), portal vein pressure decreased from 9.0 +/- 0.5 to 8.5 +/- 0.5 mmHg (P < 0.0001), portal flow increased from 637 +/- 49 to 668 +/- 60 ml/min (P = 0.09), and transhepatic resistance decreased from 7.5 +/- 1.5 to 6.5 +/- 1.0 mmHg.min.l-1 (P < 0.01), but cardiac output was unchanged (1,929 +/- 126 to 1,890 +/- 138 ml/min). Total splanchnic intravascular volume (VI) increased 1.6 +/- 1.0% (P < 0.05, 14 +/- 10 ml). This increase was due to an increment in extrahepatosplenic (mesenteric) VI (12.9 +/- 1.9%, P < 0.0001), since splenic VI decreased (9.6 +/- 2.8%, P < 0.0001) and hepatic VI did not change. After splenectomy, nitroglycerin infusions at doses of 0.5 and 2 mg/min were associated with increases in total splanchnic VI of 3.7 +/- 1.2% (P < 0.0001, 30 +/- 10 ml) and 7.6 +/- 1.7% (P < 0.001, 59 +/- 10 ml) due entirely to increases in mesenteric volume of 9.9 +/- 2.7% (P < 0.0001) and 16.5 +/- 1.9% (P < 0.0001), respectively, but cardiac output was unchanged at the end of infusion at either dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Reflex effects of left atrial pressure elevation on total intravascular volume.

The reflex autonomic influence of left atrial baroreceptor stimulation on the total capacitance vasculature has not been examined. To this end, left atrial pressure was increased in 25 anesthetized dogs, in which blood from the vena cavae was drained into an extracorporeal reservoir and returned to the right atrium at a constant rate, so that changes in intravascular volume could be recorded as reciprocal changes in reservoir volume. Left atrial pressure was elevated from 5 +/- 1 (mean +/- SE) to 11 +/- 1 mmHg by inflating a balloon at the mitral orifice for 12-20 min. With left atrial pressure elevation, total intravascular volume decreased 25 +/- 10 ml (P less than 0.025). In six of the dogs, intravascular volume decreased 37 +/- 12 ml with left atrial pressure elevation before bilateral cervical vagectomies and increased 66 +/- 8 ml with atrial pressure elevation after vagectomies (P less than 0.001). In eight of the dogs, volume decreased 42 +/- 19 ml with atrial pressure elevation before propranolol administration and increased 44 +/- 29 ml after propranolol (P less than 0.03). Phenoxybenzamine in five of the animals and atropine in three did not attenuate the change in intravascular volume with left atrial pressure elevation. Thus left atrial baroreceptor stimulation is associated with an autonomic reflex, which acts to decrease intravascular volume. The afferent limb is mediated by the vagi, and the efferent limb, by beta-adrenergic receptor stimulation.

Muscarinic regulation of pulmonary intravascular volume in isolated canine lungs.

The influence of acetylcholine on pulmonary intravascular volume has not been clearly identified. In 14 anesthetized dogs, the pulmonary circulation was separately perfused in situ at a constant rate and drained to an extracorporeal reservoir, so that changes in total pulmonary intravascular volume could be recorded as reciprocal changes in reservoir volume. In eight animals, acetylcholine at 100 micrograms/min for 20 min was associated with increases in pulmonary intravascular volume (PIV) and pulmonary arterial pressure of 41 +/- 5 (SE) ml (P less than 0.001) and 2.0 +/- 0.0 mmHg (P less than 0.001; 11 infusions), respectively. These responses were abolished after atropine (6 infusions). In six animals, pulmonary venous pressure was also measured, so that total pulmonary (TPR), pulmonary arterial (PAR), and pulmonary venous (PVR) resistances could be calculated. TPR and PVR increased from 21 +/- 2 to 24 +/- 3 (P less than 0.001) and from 7 +/- 1 to 11 +/- 1 mmHg.min.l-1 (P less than 0.001), respectively, while PAR did not change significantly (6 infusions). In three of the six animals, these changes were abolished by atropine (6 infusions). In the other three animals, PIV increased 56 +/- 11 ml (P less than 0.001) before and 47 +/- 6 ml (P less than 0.001) after indomethacin. The acetylcholine-associated increases in TPR and PVR were also not significantly attenuated after indomethacin. Hence, muscarinic receptor stimulation with acetylcholine is associated with an increase in pulmonary intravascular volume, which is mediated by an increase in resistance to pulmonary venous outflow. These changes are not due to release of prostanoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of vasopressin on systemic capacity.

To assess the effect of vasopressin (VP) on systemic capacity (SC), blood was drained from the venae cavae to an oxygenator and returned to the aorta at a constant rate so that changes in SC could be measured as the inverse of changes in oxygenator volume in 17 anesthetized pigs. After 10 min of VP administration (1.1 U/min ia), mean arterial pressure increased from 67 +/- 2 to 144 +/- 7 mmHg (P less than 0.001). SC decreased promptly and reached a nadir of 110 +/- 32 ml (P less than 0.02, 5.5 ml/kg) below control at 5 min but returned to 35 +/- 65 ml (P = not significant, 1.8 ml/kg) below control at 10 min. Portal venous pressure decreased from 19.3 +/- 2.6 to 16.6 +/- 2.7 mmHg (P less than 0.001), and portal flow decreased from 828 +/- 68 to 458 +/- 92 ml/min (P less than 0.001). Transhepatic venous resistance increased. After evisceration, VP caused only an increase in SC. Thus VP causes an initial SC decrement due entirely to a decrease in splanchnic capacity. The decrease in splanchnic capacity must be caused, at least in part, by the decrease in gastrointestinal arterial inflow and subsequent decrease in portal venous pressure. These initial effects of VP on SC would be expected to enhance ventricular filling and cardiac output in the intact animal and could be important in the acute compensatory response to hemorrhage.

Influence of serotonin on total intravascular capacity in the anaesthetized dog.

The influence of serotonin on intravascular volume in the total capacitance circulation has not previously been examined. Thus, blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that total intravascular volume changes could be recorded as the inverse of changes in reservoir volume in 31 anaesthetized dogs. Serotonin (588 +/- 47 micrograms) in the left atrium was associated with an initial decrease in intravascular volume of 39 +/- 12 ml (P less than 0.01) followed by an increase of 129 +/- 31 ml (P less than 0.01) above control at 20 min. Mean arterial pressure increased from a control of 74 +/- 4 mmHg to 99 +/- 7 mmHg (P less than 0.01) initially and then decreased to 64 +/- 5 mmHg (P less than 0.05) at 20 min. Following ganglionic blockade with mecamylamine, serotonin caused only a decrease in intravascular volume, which was 73 +/- 12 ml (P less than 0.01) at 20 min. 5-HT2 and alpha-adrenergic blockade with ketanserin did not attenuate the early decrease in intravascular volume. 5-Carboxamidotryptamine (82 +/- 39 micrograms), a 5-HT1 agonist, was associated with only an increase in intravascular volume, which was 82 +/- 13 ml (P less than 0.01) at 20 min and which was abolished after ganglionic blockade. Thus, serotonin causes a biphasic change in total intravascular volume. The initial decrease in intravascular volume is not mediated by a reflex or by 5-HT1, 5-HT2, or alpha-adrenergic receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative radionuclide assessment of total pulmonary vascular volume changes.

Current techniques do not permit continuous and noninvasive assessments of changes in total pulmonary intravascular volume. Hence, the present study was undertaken to determine whether quantitative radionuclide imaging can be used to determine the direction and estimate the magnitude of total pulmonary vascular volume changes. The pulmonary circulation was separately perfused at a constant rate via the pulmonary artery and drained at a constant pressure via the left atrium in nine dogs. Changes in pulmonary intravascular volume were recorded as reciprocal changes in extracorporeal reservoir volume during phenylephrine or isoproterenol administration, a 20% increase in pulmonary artery flow or a 5 mmHg (1 mmHg = 133.32 Pa) decrease in left atrial pressure. Erythrocytes were labeled with technetium-99m and pulmonary volume changes were determined from tissue attenuation, blood radioactivity, and changes in total pulmonary radioactivity obtained with a gamma-camera. During each of the interventions, count changes correlated with volume changes (r greater than or equal to 0.75). The technique reliably detected volume changes as small as 10 mL. For all 531 individual pairs of radionuclide- and reservoir-determined volume changes, the correlation between reservoir-determined and radionuclide-estimated pulmonary intravascular volume changes was 0.87. The standard error of the radionuclide estimate was 21 mL. Hence, the present study demonstrates that quantitative radionuclide imaging can be used to continuously and noninvasively determine total pulmonary vascular volume changes.

Influence of the new inotropic agent DPI 201-106 on the total capacitance vasculature in dogs.

Recent investigations have demonstrated that the piperazinyl-indole DPI 201-106 (DPI) acts to increase contractility independent of increases in cAMP or inhibition of Na+, K(+)-ATPase. Since associated changes in the capacitance vasculature would also be expected to influence ventricular performance, the influence of DPI on total intravascular volume (IV) was examined. In eight anesthetized dogs undergoing prior sinoaortic baroreceptor denervation and bilateral cervical vagotomy, blood from the venae cavae was drained to an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in IV could be recorded as reciprocal changes in reservoir volume. Racemic DPI at 50 micrograms/kg/min for 20 min was associated with a 65 +/- 7 ml (P less than 0.0001) decrease in total IV and a decrease in mean arterial pressure from 80 +/- 7 to 74 +/- 5 mmHg (P less than 0.0001). DPI administration was associated with a 67 +/- 9 ml (P less than 0.05) decrease in IV after beta adrenergic blockade and a 68 +/- 11 ml (P less than 0.05) decrease in IV after alpha and beta adrenergic blockade. Abdominal evisceration abolished the IV decrement due to DPI. Radionuclide imaging studies demonstrated that decreases in hepatic and splenic IV contributed to the decrease in splanchnic IV. Thus, DPI acts to decrease total IV. The IV decrement is due entirely to a decrease in splanchnic IV and is not mediated by baroreceptor stimulation or by adrenergic receptor stimulation. In the animal with an intact circulation, the total IV decrement would be expected to increase venous return and thereby act to maintain ventricular end diastolic pressure.

Effects of beta-adrenergic agonists on splanchnic vascular volume and cardiac output.

The effect of beta-adrenergic agonists on splanchnic intravascular volume (SIV), measured with radionuclide imaging, and the subsequent influence of such volume changes on cardiac output (CO) were examined in 40 anesthetized dogs. Isoproterenol (6 micrograms/min) caused a decrease in total SIV of 12 +/- 1% (P less than 0.001). The decrease was due entirely to a decrease in splenic volume of 24 +/- 3% (P less than 0.001), since volume increased in the remainder of the splanchnic vasculature [hepatic and mesenteric volume increased 12 +/- 2% (P less than 0.001) and 11 +/- 3% (P less than 0.02), respectively]. CO increased from 1,724 +/- 187 to 3,138 +/- 321 ml/min (P less than 0.001); after subsequent splenectomy, isoproterenol caused a similar increment. Isoproterenol-associated SIV changes were not altered by carotid denervation and vagotomy or by beta 1-adrenergic inhibition with metoprolol but were abolished by nonselective beta-adrenergic inhibition with propranolol. With a larger dose of metoprolol and smaller dose of isoproterenol to minimize beta 1-adrenergic effects, the isoproterenol-associated CO increment was attenuated (P less than 0.01) by splenectomy. With the beta 2-agonist terbutaline (41 micrograms/min) after metoprolol, total SIV decreased 15 +/- 4% (P less than 0.001). After subsequent alpha-adrenergic inhibition with phenoxybenzamine, terbutaline caused no change in SIV and an attenuated (P less than 0.05) increase in CO. Thus beta-adrenergic agonist administration causes a decrease in total SIV due entirely to a decrease in splenic volume. The SIV decrement is dependent on beta 2- and alpha-adrenoceptor stimulation and appears to enhance CO only if beta 1-adrenergic effects are minimized.

The role of the splanchnic circulation in the regulation of total intravascular volume during alpha adrenergic receptor stimulation.

Previous studies have not defined the contribution of the splanchnic circulation to the total intravascular volume change associated with selective alpha adrenergic receptor stimulation. Since the splanchnic circulation is responsible for the total volume changes associated with other types of selective autonomic receptor stimulation, the present study was undertaken to examine the influence of alpha adrenergic receptor stimulation on splanchnic intravascular volume, the hemodynamic mechanism responsible for the splanchnic volume change, and the contribution of the splanchnic volume change to the change in total volume. In 35 anesthetized dogs, blood from the vena cavae was drained into an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in total intravascular volume could be measured as reciprocal changes in reservoir volume. Phenylephrine infusion (100 micrograms/min) for 20 min in 28 dogs was associated with a decrease in total volume of 64 +/- 17 (SEM) ml (P less than 0.0001). The response was abolished by either alpha adrenergic blockade or evisceration but was not attenuated by beta adrenergic blockade, sinoaortic baroreceptor denervation, ganglionic blockade, or splenectomy. In 5 animals with separate splanchnic perfusion and drainage, total and splanchnic volumes decreased 59 +/- 8 ml (P less than 0.0001) and 317 +/- 20 ml (P less than 0.0001), respectively, while transhepatic vascular resistance increased 17 +/- 4 cm H2O X min/l (P less than 0.0001). These responses were abolished after alpha adrenergic blockade. Thus, splanchnic volume decreases with alpha adrenergic receptor stimulation, despite an increase in hepatic resistance to splanchnic venous outflow. The splanchnic volume decrement is entirely responsible for the total volume decrement.

Effects of hemodynamic variables on myocardial K+ balance during and after shortlasting ischemia.

Ischemia-induced myocardial potassium loss and post-ischemic potassium reuptake was quantitated in 8 open chest pigs during control conditions and during hemodynamic alterations which have been shown to increase steady state sarcolemmal potassium fluxes. Myocardial K+ balance was continuously computed before, during and after a 90 s occlusion of a branch of the circumflex artery during control (CTR), during pacing tachycardia (PACE: 34% increase in heart rate), during proximal aortic constriction (AC; 28% increase in LVSP), and during isoprenaline infusion (ISO; 135% increase in LVdP/dt and 35% increase in heart rate). Ischemia-induced potassium loss increased significantly (40%) during ISO only. Higher basal metabolic rate, increased sarcolemmal K+ conductance, or ischemia-induced depression of a more active Na/K-pump during ISO are possible explanations to why increased K+ loss appeared in this situation. The maximal rate of post-ischemic potassium reuptake was not different from CTR during PACE and ISO, but it was reduced during AC, which might be due to persisting subendocardial ischemia in early reperfusion when ventricular wall stress is high. The extent of potassium restoration was not different from CTR during AC, PACE and ISO.

Influence of verapamil on total and regional intravascular volume in dogs.

Verapamil's influence on intravascular volume (IV) in the total capacitance circulation was examined in anesthetized dogs after mecamylamine or baroreceptor denervation. Blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that IV changes could be measured as reciprocal changes in reservoir volume. In 10 dogs, verapamil (50 micrograms/min) caused a decrease in total IV of 74 +/- 12 ml (P less than 0.0005) at 20 min and a decrease in arterial pressure from 79 +/- 5 to 66 +/- 3 mmHg (P less than 0.0005). After evisceration in nine animals, verapamil caused an extrasplanchnic (XSPL) IV decrease of 97 +/- 19 ml (P = 0.08). In 11 animals with separate perfusion and drainage of the splanchnic and XSPL circulations, verapamil caused an XSPL IV decrease of 74 +/- 20 ml (P less than 0.002) and a splanchnic IV increase of 19 +/- 9 ml (P = 0.06). In four animals on cardiopulmonary bypass, IV decreased 154 +/- 66 ml (P less than 0.002) during verapamil administration. Thus total IV decreases due to a decrease in systemic extrasplanchnic volume. Because pressure decreased while arterial flow and venous outflow pressure were constant, a decrease in the resistance to blood return to the central circulation mediates the XSPL volume decrement.

Radionuclide assessment of peripheral intravascular capacity: a technique to measure intravascular volume changes in the capacitance circulation in man.

Changes in the capacitance vasculature influence venous return and cardiac performance, so an understanding of the effects of pathophysiologic states on the human capacitance vasculature is necessary to understand integrated cardiovascular function in man. Techniques available to assess the capacitance vasculature in man, however, have limitations. We performed radionuclide imaging of the calf or forearm in 51 patients whose erythrocytes had been labeled in vivo with technetium-99m, basing our approach on the principle that counts from the radiolabeled intravascular space are proportional to blood volume. Two-minute or 15 second count acquisitions were obtained from the calf in 42 patients. Counts obtained at rest demonstrated little variation. With veno-occlusion at 15 and 30 mm Hg, counts increased 8 +/- 1% (+/- SEM) (p less than 0.001) and 28 +/- 2% (p less than 0.001), respectively. After 0.4 mg of sublingual nitroglycerin, counts increased 9 +/- 1% (p less than 0.001). With leg elevation, counts decreased 34 +/- 4% (p less than 0.001). Response patterns were similar with 2-minute and 15-second acquisitions. In nine patients who underwent forearm imaging (2-minute acquisitions), counts increased 14 +/- 2% (p less than 0.001) and 26 +/- 4% (p less than 0.001) at 15- and 30-mm Hg veno-occlusion and 15 +/- 3% (p less than 0.001) after nitroglycerin. Volume displacements, recorded simultaneously with a fluid-filled plethysmograph about the contralateral forearm, correlated linearly in all nine patients. Thus, gamma camera imaging of the radiolabeled peripheral intravascular space provides a quantitative and reliable assessment of peripheral vascular capacity in man. The technique could be used in conjunction with gated cardiac imaging in order to assess the interactions of peripheral vascular capacity and ventricular performance.

The role of the liver in the adrenergic regulation of blood flow from the splanchnic to the central circulation.

Cardiac output is determined, in large part, by the venous return of blood to the heart. Various adrenergic and pharmacologic influences affect venous return. In the dog it appears that the liver may play an important role in the control of blood flow from the splanchnic to the central circulation and, hence, in the control of venous return.

Regulation of splanchnic organ size during muscarinic receptor stimulation in the anaesthetized pig.

To determine the mechanisms responsible for changes in splanchnic organ size during muscarinic receptor stimulation, acetylcholine was infused at 5 micrograms kg-1 min-1 in 11 anaesthetized pigs which had previously undergone carotid denervation and cervical vagotomy. Blood pressure decreased by 42 +/- 4 mmHg (P less than 0.005), portal vein pressure decreased by 1.0 +/- 0.3 mmHg (P less than 0.01), IVC pressure increased by 0.2 +/- 0.1 mmHg (P less than 0.01), hepatic arterial flow increased by 10 +/- 6 ml min-1 (NS), portal vein flow decreased by 89 +/- 20 ml min-1 (P less than 0.005), splenic segment length (SSL) decreased by 0.52 +/- 0.11 mm (P less than 0.005) (control 12.49 +/- 1.27) (measured with ultrasonic crystals) and hepatic segment length (HSL) increased by 0.29 +/- 0.06 mm (P less than 0.005) (control 13.94 +/- 1.16). Aortic constriction to decrease the splanchnic distending pressure by an amount comparable to that achieved with the acetylcholine-associated decrease in portal flow caused a similar decrease in SSL and increase in HSL. Graded constriction of the portal vein or IVC, to increase SSL or HSL respectively, in the presence and absence of acetylcholine demonstrated no change in splenic or hepatic compliance with acetylcholine. Ligation of the splenic vasculature reduced the acetylcholine-associated HSL increase from 0.41 +/- 0.09 to 0.20 +/- 0.07 mm (P less than 0.05). Acetylcholine infused directly into the portal vein did not alter HSL. Atropine abolished all acetylcholine-associated haemodynamic changes. Thus, muscarinic receptor stimulation does not appear to act directly on splanchnic capacity vessels. Splenic dimension decreases due to a decrease in splanchnic flow and pressure, and hepatic dimension increases due to an increase in IVC pressure and redistribution of volume from the spleen.