Unstressed Vascular Volume Research Articles

Role of splanchnic constriction in governing the hemodynamic responses to gravitational stress in conscious dogs

Octreotide is a somatostatin analog that constricts the splanchnic circulation, thereby improving orthostatic tolerance. We tested the hypotheses that octreotide improves orthostatic tolerance by 1)increasing cardiac filling (right atrial) pressure via reductions in vascular capacity; 2) by causing an upward (i.e., cranial) shift of the hydrostatic indifferent point; and 3) by increasing arterial pressure via a reduction in total vascular conductance. Studies were carried out in acepromazine-sedated, hexamethonium-treated atrioventricular-blocked conscious dogs lightly restrained in lateral recumbency. Beat-by-beat cardiac output was held constant via computer-controlled ventricular pacing at rest and during 30 s of 30° head-up tilt. Octreotide (1.5 μg/kg iv) raised right atrial pressure by 0.5 mmHg and raised mean arterial pressure by 11 mmHg by reducing total vascular conductance (all P < 0.05). Right atrial pressure fell by a similar amount in response to tilting before and after octreotide, thus there was no difference in location of the hydrostatic indifferent point. These data indicate that octreotide improves orthostatic tolerance by decreasing total vascular conductance and by increasing cardiac filling pressure via a reduction in unstressed vascular volume and not by eliciting a cranial shift of the location of the hydrostatic indifferent point.

Control of Cardiac Output

Abstract Although cardiac output is measured as the flow of blood from the left ventricle into the aorta, the system that controls cardiac output includes many other components besides the heart itself. The heart’s rate of output cannot exceed the rate of venous return to it, and therefore, the factors governing venous return are primarily responsible for control of output from the heart. Venous return is affected by its pressure gradient and resistance to flow throughout the vascular system. The pressure gradient for venous return is a function of several factors including the blood volume flowing through the system, the unstressed vascular volume of the circulatory system, its capacitance, mean systemic pressure, and right atrial pressure. Resistance to venous return is the sum of total vascular resistance from the aortic valve to the right atrium. The sympathetic nervous system and vasoactive circulating hormones affect short-term resistance, whereas local tissue blood flow autoregulatory mechanisms ar...

Theoretical analysis of the noncardiac limits to maximum exercise.

When right atrial pressure (Pra) is greater than zero (atmospheric pressure), cardiac output is determined by the intersection of two functions, cardiac function and return function, which is used here to mean the determinants of venous return. When Pra < or = 0, flow is only determined by circuit function. The objective of this analysis was to determine the potential changes in return function that need to occur to allow the maximum cardiac output during exercise when Pra < or = 0 or is constant. The analysis expands on the model of Green and Jackman and includes the effects of changes in circuit parameters, including venous resistance, changes in capacitance, and muscle contractions. The analysis is based on the model of the circulation proposed by Permutt and co-workers, which assumes that the systemic circulation has two lumped compliant regions in parallel with independent inflow and outflow resistances. Changes in total flow in this model can come about by changes in the distribution of flow between the regions, recruitment of unstressed vascular volume, and changes in the regional venous resistances. The data for the analysis are from previous animal studies and are normalized to a 70-kg man. The major conclusions are that, to achieve the high cardiac output that occurs at peak exercise, there need to be marked changes in the distribution of blood flow, recruitment of unstressed volume, and the venous resistance draining vascular beds. A consequence of the increase in peripheral flow is a marked increase in pressure in the veins of the working muscle. Muscle contractions are potentially a very important mechanism for transiently decreasing this pressure and preventing excessive filtration of plasma during exercise.

Hindlimb unweighting affects rat vascular capacitance function.

Microgravity is associated with an impaired stroke volume and, therefore, cardiac output response to orthostatic stress. We hypothesized that a decreased venous filling pressure due to increased venous compliance may be an important contributing factor in this response. We used a constant flow, constant right atrial pressure cardiopulmonary bypass procedure to measure total systemic vascular compliance (C(T)), arterial compliance (C(A)), and venous compliance (C(V)) in seven control and seven 21-day hindlimb unweighted (HLU) rats. These compliance values were calculated under baseline conditions and during an infusion of 0.2 microg*kg(-1)*min(-1) norepinephrine (NE). The change in reservoir volume, which reflects changes in unstressed vascular volume (DeltaV(0)) that occurred upon infusion of NE, was also measured. C(T) and C(V) were larger in HLU rats both at baseline and during the NE infusion (P < 0.05). Infusion of NE decreased C(T) and C(V) by ~20% in both HLU and control rats (P < 0.01). C(A) was also significantly decreased in both groups of rats by NE (P < 0.01), but values of C(A) were similar between HLU and control rats both at baseline and during the NE infusion. Additionally, the NE-induced DeltaV(0) was attenuated by 53% in HLU rats compared with control rats (P < 0.05). The larger C(V) and attenuated DeltaV(0) in HLU rats could contribute to a decreased filling pressure during orthostasis and thus may partially underlie the mechanism leading to the exaggerated fall in stroke volume and cardiac output seen in astronauts during an orthostatic stress after exposure to microgravity.

The effects of hindlimb unweighting on the capacitance of rat small mesenteric veins.

Microgravity is associated with an impaired cardiac output response to orthostatic stress. Mesenteric veins are critical in modulating cardiac filling through venoconstriction. The purpose of this study was to determine the effects of simulated microgravity on the capacitance of rat mesenteric small veins. We constructed pressure-diameter relationships from vessels of 21-day hindlimb-unweighted (HLU) rats and control rats by changing the internal pressure and measuring the external diameter. Pressure-diameter relationships were obtained both before and after stimulation with norepinephrine (NE). The pressure-diameter curves of HLU vessels were shifted to larger diameters than control vessels. NE (10(-4) M) constricted veins from control animals such that the pressure-diameter relationship was significantly shifted downward (i.e., to smaller diameters at equal pressure). NE had no effect on vessels from HLU animals. These results indicate that, after HLU, unstressed vascular volume may be increased and can no longer decrease in response to sympathetic stimulation. This may partially underlie the mechanism leading to the exaggerated fall in cardiac output and stroke volume seen in astronauts during an orthostatic stress after exposure to microgravity.

Renin Angiotensin System Antagonists and Anesthesia

R enin angiotensin system (RAS) antagonists, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor antagonists are increasingly used to treat cardiovascular and other diseases (1–6). These treatments induce a blockade of the RAS that may affect hemodynamics during anesthesia and surgery. In 1978, Miller et al. (7) reported that the RAS is involved in maintaining normal blood pressure during anesthesia. Although anesthesia is not invariably associated with a deleterious hemodynamic event in RAS-blocked patients (8–10), hemodynamic instability, described as unexpected episodes of hypotension, have been reported (11–13). Otherwise, stresses such as surgery or hypotension stimulate the generation of angiotensin II, which induces vasoconstriction (14) to maintain blood pressure but reduces blood flow to organs such as the kidneys and bowels. Accordingly, an angiotensin II-induced reduction in blood flow may contribute to acute renal failure (15) and splanchnic ischemia (16), which are obvious factors in postoperative morbidity (17). RAS blockade with ACE inhibitors decreases some consequences of the stress response on the regional circulation (9,18,19), which may then contribute to body protection. Much of the information regarding the physiology and pathophysiology of the RAS during anesthesia and surgery is based on the effects of ACE inhibitors. Because ACE inhibitors probably act mostly by blocking the RAS, similar effects should be obtained from angiotensin (AT) receptor antagonists. RAS antagonist pharmacology may help us to understand the hemodynamic risk of anesthesia in RAS-blocked patients, to identify predisposing factors, and to determine the potential benefit of RAS antagonists during anesthesia and surgery. Physiology of the RAS Generation of Angiotensin II

Renal size and composition in hypertensive, obese rabbits.

To determine whether the renal growth associated with obesity is due to hypertrophy or hyperplasia. New Zealand white female rabbits were fed either standard rabbit chow (n=17) or chow fortified with 10% corn oil plus 5% lard (n=18) for 12-16 weeks. All rabbits were weighed, and intra-arterial blood pressures were successfully measured at the end of the study in 16 lean and 18 obese rabbits; percent water of entire kidneys (8 lean, 8 obese rabbits) and of defined regions of kidneys (8 lean, 10 obese rabbits) were obtained gravimetrically. Renal hemoglobin, protein and DNA was measured chemically (8 lean, 8 obese rabbits). Kidneys grew in size as the rabbits gained fat. In a series of 8 lean and 8 age-matched obese rabbits, weighing 3.7+/-0.1 kg and 5.4+/-0.4kg (P<0.05), the kidneys were 20% larger in the obese rabbits: 15.0+/-0.9 g vs 18.0+/-2.5 g (P<0.05). Kidney protein was also 20% greater in the obese rabbit: 1.38+/-0.06 g/kidney vs 1.66+/-0.06 g/kidney (P<0.05). While total renal DNA was 16% greater in the obese: 18.2+/-0.5 microg/kidney vs 21.1+/-0.61 g/kidney (P<0.05), no significant difference existed when the DNA was expressed as microg/mg protein. Fractional water content of the intact kidney declined with obesity: 78.7+/-1.1% vs 76.0+/-1.2% (P<0.05). Conversely, the hemoglobin content of the kidney at autopsy, an estimate of the unstressed vascular volume, increased with obesity: 55+/-19 mg/kidney vs 82+/-25 mg/kidney (P<0.05). By contrast, water content of renal parenchyma was constant: 80.8+/-1.0% vs 80.9+/-1.2% (cortex); 84.0+/-0.8% vs 83.6%+/-2.0% (outer medulla); and 85.7+/-0.8% vs 86.0+/-2.1% (inner medulla). The renal growth associated with obesity was predominantly hyperplastic and was associated with a partial exclusion of fluid from the renal sinus.

Clinical death and the measurement of stressed vascular volume.

To measure stressed vascular volume in humans and to review the concepts of stressed and unstressed vascular volume. Observational study during surgical procedure. Operating room at a university hospital. Five patients undergoing hypothermic circulatory arrest for surgery on major vessels. We measured the volume that drained from the patient to the reservoir of the pump when the pump was turned off. Stressed volume was 20.2+/-1.0 mL/kg, which is 30% of the predicted blood volume of these patients. The amount of blood volume that determines vascular filling pressure is only about a quarter of the total predicted volume, which means that there is a large reserve of unstressed volume that can be recruited to maintain vascular filling pressure.

Effect of pregnancy on pressure-volume relationships in circulation of rabbits

Mean circulatory filling pressure (MCFP) has been measured after vagally induced cardiac arrest in 11 nonpregnant and 10 near-term pregnant rabbits, anesthetized with pentobarbital sodium. MCFP was 6.1 +/- 0.4 (SD) mmHg in the nonpregnant and 7.2 +/- 0.4 mmHg in the pregnant animals. The difference of 1.1 mmHg was significant (P < 0.001). Sympathetic blockade with bretylium tosylate (10 mg/kg) reduced MCFP by 0.4 mmHg in both nonpregnant and pregnant rabbits. Vascular capacitance was examined in the two groups. Unstressed vascular volume and vascular compliance were derived from measurements of MCFP after increasing blood volume by 8 and 16% or reducing it by 8%. The unstressed vascular volumes, 33.9 +/- 3.9 (SD) ml/kg in the nonpregnant and 35.1 +/- 3.2 ml/kg in the pregnant group, were not significantly different, but compliance in the pregnant group (4.0 +/- 0.6 ml.kg-1.mmHg-1) was significantly greater than in the nonpregnant rabbits (3.4 +/- 0.6 ml.kg-1.mmHg-1) (P < 0.05). We conclude that there are changes in vascular capacitance in rabbit pregnancy, probably not related to alterations in vasomotor activity, but these are insufficient to fully compensate for the increase in blood volume, thus leading to the rise in MCFP.

Alpha- and beta-adrenergic mechanisms in the control of vascular capacitance by the carotid sinus baroreflex system.

We examined the active and passive contributions of the alpha- and beta-adrenergic receptor mechanisms to the changes in systemic vascular capacitance caused by the carotid sinus baroreflex system in anesthetized, vagotomized dogs. The carotid sinuses were isolated from the systemic circulation and perfused with controlled pressures. To determine the changes in vascular capacitance, a constant flow, constant venous pressure cardiopulmonary bypass was used. The changes in unstressed vascular volume were calculated when carotid sinus pressure was reduced from 200 to 50 mmHg without any adrenergic receptor antagonist, with either an alpha- (phentolamine) or a beta- (propranolol) antagonist and then with both. The reflex change in unstressed vascular volume in the systemic circulation (22.6 +/- 9.0 ml/kg without any antagonist) was reduced by 72% with phentolamine, by 35% with propranolol, and by 73% with both antagonists. Our results suggest that the alpha-adrenergic mechanisms contribute significantly to active changes in systemic venous capacity. In addition, the beta-adrenergic system has very little effect on active changes in venous vessels but does contribute to the overall capacity changes by dilating the hepatic outflow resistance when the carotid sinus baroreflex system is activated.

Effect of enalaprilat on splanchnic vascular capacitance during acute ischemic heart failure in dogs

This study investigates the effect of angiotensin-converting-enzyme inhibition by intravenous enalaprilat (100 micrograms/kg) on splanchnic vascular capacitance during acute left ventricular failure induced by coronary microembolization in alpha-chloralose/urethan anesthetized dogs. Changes in hepatic and splenic vascular volumes were determined from organ diameters (sonomicrometry) at 15, 30, and 45 min after enalaprilat injection. Changes in vascular capacitance were assessed from organ pressure-diameter curves obtained during transient hepatic outflow occlusion. Thirty minutes after enalaprilat, hepatic volume was increased by 52 +/- 14 ml (P < 0.01), and portal and hepatic vein pressures were decreased from 10.2 +/- 0.9 to 8.7 +/- 0.8 mmHg (P < 0.01) and from 3.9 +/- 1.6 to 3.1 +/- 0.7 mmHg (P < 0.05), respectively. Splenic volume did not change. Enalaprilat shifted the hepatic pressure-diameter curve upward, resulting in a larger hepatic volume at any given pressure. Curve intercept was increased, suggesting an increase in unstressed vascular volume. Curve slope was unchanged. In conclusion, enalaprilat increased hepatic vascular volume during acute left ventricular failure in dogs. The pressure-diameter curve shift suggests a reduction in the smooth muscle tone of hepatic capacitance vessels.

Effects of Nitroglycerin and Nitroprusside on Vascular Capacitance of Anesthetized Ganglion-Blocked Dogs

To determine whether changes in vascular capacitance induced by nitroglycerin (NTG) and nitroprusside were due to changes in compliance or unstressed vascular volume, doses producing similar reductions in arterial pressure (Psa) were studied on separate days in six dogs anesthetized and ventilated with pentobarbital after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline blood volumes and after increases of 5 and 10 ml/kg. Central blood volumes (CBVs, pulmonary artery to aortic root) were determined from transit times, and separately measured cardiac output (CO) was estimated by thermodilution (right atrium to pulmonary artery). NTG and nitroprusside produced similar reductions in Psa and Pmcf without significantly altering right atrial pressure (Pra), pressure gradient for venous return, or CO. Total vascular compliance was not altered, but total vascular capacitance was increased on an average of 4.0 +/- 1.4 ml/kg after NTG and 3.0 +/- 1.3 ml/kg after nitroprusside by increases in unstressed volume. Both drugs caused a variable reduction in CBV, averaging 2 ml/kg. Thus, both drugs produced a large increase in peripheral venous capacitance by increasing unstressed vascular volume without altering total vascular compliance.

Arginine vasopressin increases apparent whole body capacity in anesthetized cats

The effects of arginine vasopressin (AVP) on capacitance function were assessed in anesthetized cats by draining blood from the superior and inferior venae cavae into an external reservoir and then returning blood to the right atrium at a constant rate. Under these conditions, changes in reservoir volume were assumed to reflect reciprocal changes in whole body capacity. Intravenous infusions of AVP (1, 10, and 100 ng.kg-1.min-1) that elevated plasma AVP concentrations by approximately 30, 400, and 4,000 fmol/ml were associated with concentration-dependent increases in whole body capacity that ranged between 1.6 and 8 ml/kg. In contrast to AVP, intravenous infusions of angiotensin II (5, 10, and 50 ng.kg-1.min-1) had relatively little influence on capacity, whereas norepinephrine administration (300, 1,000, and 3,000 ng.kg-1.min-1) was associated with dose-dependent decreases in capacity of 4.5-10.3 ml/kg. Virtually the entire increase in whole body capacity to AVP can be accounted for by summation of the predicted contributions of an active reflex venodilatatory component and those of a passive component (arterial and cardiopulmonary compartments). Because systemic compliance (delta reservoir volume/delta venous pressure) was not changed by AVP administration, the contribution of a reflex venodilatatory component must be the result of increases in unstressed vascular volume (contained volume at 0 transmural pressure) as opposed to changes in compliance. These results may explain why AVP decreases cardiac output to a greater extent than either angiotensin II or sympathomimetics and, thus, why AVP is a weaker pressor agent in animals with intact autonomic function.

Atrial natriuretic peptide reverses angiotensin-induced venoconstriction in dogs

To determine whether atrial natriuretic peptide (ANP) can reverse angiotensin (ANG II)-induced venoconstriction, ANP was infused (0.3 micrograms.kg-1.min-1) in the presence of ANG II-induced hypertension in six ganglion-blocked dogs. ANG II was initially administered to increase mean arterial blood pressure (MAP) 50% above control. ANG II did not change heart rate or left ventricular rate of pressure development (LV dP/dt) but increased total peripheral vascular resistance (TPVR) and left ventricular end-diastolic pressure (LVEDP). Mean circulatory filling pressure (MCFP) increased, whereas cardiac output and venous compliance decreased. Unstressed vascular volume did not change, but central blood volume increased. ANP infusion during ANG II-induced hypertension resulted in a decrease in MAP, but TPVR did not change. There were no changes in heart rate or LV dP/dt. ANP decreased cardiac output further. LVEDP returned to base line with ANP. ANP also decreased MCFP and normalized venous compliance. There was no significant change in total blood volume, but central blood volume decreased. In summary, ANP can reverse the venoconstriction but not the arterial vasoconstriction produced by ANG II. The decrease in MAP was due to a decrease in cardiac output that resulted from venodilatation and aggravation of the preload-afterload mismatch produced by ANG II alone. Because TPVR did not change when MAP fell, we conclude that the interaction between ANG II and ANP occurs primarily in the venous circulation.

Mechanism for decrease in cardiac output with atrial natriuretic peptide in dogs

To examine the mechanism by which atrial natriuretic peptide (ANP) decreases cardiac output, we studied changes in the heart, peripheral circulation, and blood flow distribution in eight dogs. ANP was given as a bolus (3.0 micrograms/kg) followed by an infusion of 0.3 microgram.kg-1.min-1. ANP did not change heart rate, total peripheral vascular resistance, and the first derivative of left ventricular pressure but decreased mean aortic pressure from 91 +/- 4 to 76 +/- 3 mmHg (P less than 0.001) and cardiac output from 153 +/- 15 to 130 +/- 9 ml.kg-1.min-1 (P less than 0.02). Right atrial pressure and left ventricular end-diastolic pressure also decreased. Mean circulatory filling pressure decreased from 7.1 +/- 0.3 to 6.0 +/- 0.3 mmHg (P less than 0.001), but venous compliance and unstressed vascular volume did not change. Resistance to venous return increased from 0.056 +/- 0.008 to 0.063 +/- 0.010 mmHg.ml-1.kg.min (P less than 0.05). Arterial compliance increased from 0.060 +/- 0.003 to 0.072 +/- 0.004 ml.mmHg-1.kg-1 (P less than 0.02). Total blood volume and central blood volume decreased from 82.2 +/- 3.1 to 76.2 +/- 4.6 and from 19.8 +/- 0.8 to 17.6 +/- 0.6 ml/kg (P less than 0.02), respectively. Blood flow increased to the kidneys. We conclude that ANP decreases cardiac output by decreasing total blood volume. This results in a lower operating pressure and volume in the venous capacitance system with no significant venodilating effects. Cardiac factors and a redistribution of flow to the splanchnic organs are not important mechanisms to explain the decrease in cardiac output with ANP.

Vascular capacitance and reversal of 2-kidney, 1-clip hypertension in rats.

Vascular capacitance was studied in conscious early-phase (less than 6 wk) 2-kidney, 1-clip (2K, 1C) hypertension and compared with sham-clipped control rats. Two other groups of 2K, 1C rats were studied before and 6 h after unclipping or a sham operation. Mean circulatory filling pressure (MCFP) was measured during a brief circulatory arrest caused by inflation of a right atrial balloon. Blood volume (BV) was determined from plasma volume (125I-labeled albumin) and hematocrit. MCFP was measured at resting BV and after rapid BV changes. Vascular compliance was derived from the MCFP-BV curve. Hypertensive 2K, 1C rats had an increase in hematocrit (46 +/- 1.3 vs. 42 +/- 0.4%, P less than 0.01) and no difference in BV compared with controls. MCFP was increased (8.6 +/- 1.0 vs. 7.2 +/- 0.2 mmHg, P less than 0.01) with no difference in compliance, indicating decreased unstressed vascular volume in the 2K, 1C group. After unclipping, there was a significant fall in mean arterial pressure to normal, with a fall in MCFP (8.14 +/- 0.32 to 6.78 +/- 0.11 mmHg, P less than 0.01), but there was no difference in BV or compliance compared with the 2K, 1C group, indicating an increase in unstressed vascular volume after unclipping. These studies for the first time show an important role for vascular capacitance in modulating the circulatory changes accompanying the fall in blood pressure in surgical reversal of 2K, 1C hypertension.

Cardiac and peripheral circulatory responses to angiotension and vasopressin in dogs.

To determine the cardiac and peripheral circulatory responses to changes in afterload with angiotension and vasopressin, we increased mean aortic pressure 25% and 50% above control in splenectomized and ganglion-blocked dogs. We compared these responses to similar mechanical increases in aortic pressure produced by partial balloon occlusion of the descending aorta. With 25% or 50% increases in aortic pressure, angiotensin, vasopressin, and balloon inflation produced no changes in heart rate, right atrial, and mean pulmonary artery pressures. At 25% increase in aortic pressure, cardiac output was maintained with angiotensin and balloon occlusion but decreased with vasopressin. At 50% increase in aortic pressure, cardiac output was maintained with only balloon occlusion and decreased with both angiotensin and vasopressin. Whenever cardiac output fell, central blood volume did not increase as after-load increased. These changes in preload can be explained by alterations in the venous circulation. Vasopressin did not alter venous compliance or unstressed vascular volume but increased resistance to venous return. Angiotensin also increased resistance to venous return but decreased venous compliance and did not change unstressed vascular volume. Balloon occlusion had no effects on these parameters. We conclude that: (a) angiotensin caused significant venoconstriction resulting in maintenance of cardiac output at 25% but not 50% increase in aortic pressure; (b) vasopressin increased the resistance to venous return without venoconstriction; this resulted in a fall in cardiac output even with a 25% increase in aortic pressure; and (c) the effects of the agents on the venous circulation were independent of the mechanical effects of a pressure increase in the arterial circulation.

Effects of thyroid state on venous compliance and left ventricular performance in rats.

The cardiovascular system of hypothyroid, normal, and hyperthyroid rats was studied by evaluation of the peripheral venous circulation and left ventricular (LV) systolic and diastolic performance in rats. Cardiac index (CI) and CI during a volume load were measured in open-chest rats. When compared with control, hypothyroid rats showed a decrease in heart rate, aortic pressure, LV systolic pressure, first derivative for LV pressure (LV dP/dt), CI, and CI during a volume load. LV pressure-volume relation was shifted to the right, muscle stiffness was unchanged, and LV relaxation was prolonged. There was a decrease in mean circulatory filling pressure (MCFP) to 6.3 +/- 0.2 from 7.6 +/- 0.2 mmHg in control rats. This was associated with an 11% decrease in unstressed vascular volume and 12% decrease in total blood volume but no change in venous compliance. In hyperthyroid rats there was an increase in heart rate, LV systolic pressure, LV dP/dt, CI, and CI during a volume load. LV chamber stiffness was increased, but muscle stiffness and LV relaxation were unchanged. There was an increase in MCFP to 9.5 +/- 0.3 mmHg and a decrease in venous compliance to 2.65 +/- 0.12 compared with 3.20 +/- 0.09 ml.mmHg-1.kg-1 in control rats. Unstressed vascular volume and total blood volume were unchanged. In conclusion, hyperthyroid rats have augmented LV systolic function and altered diastolic function which, combined with changes in the venous circulation, result in increased venous return and thus cardiac output. In hypothyroid rats both LV systolic and diastolic function are altered. When combined with changes of the venous circulation the changes result in a decrease in cardiac output.

Development of tolerance to nitroglycerin in the arterial and venous circulation of dogs

The purpose of this study was to define the effects of nitroglycerin on venous tone and to investigate the time course of nitroglycerin tolerance in the peripheral circulation. The changes in the arterial and venous circulation resulting from an intravenous infusion of nitroglycerin (5 micrograms/kg per min) after 5 minutes (acute infusion) were compared with those changes that occurred after 2 hours (chronic infusion) of the same infusion in six splenectomized, ganglion-blocked dogs. Hemodynamics, blood volume and venous and arterial compliance were measured during each infusion. Nitroglycerin initially decreased mean arterial pressure from 81.5 +/- 2.0 to 57.6 +/- 2.7 mm Hg (p less than 0.01). Central blood volume decreased from 21.1 +/- 1.4 to 15.9 +/- 1.1 ml/kg (p less than 0.01), while total blood volume and unstressed vascular volume did not change. In the acute study, nitroglycerin increased venous compliance 33% from 1.75 +/- 0.14 to 2.32 +/- 0.16 ml/mm Hg per kg (p less than 0.01) and arterial compliance 33% from 0.049 +/- 0.007 to 0.065 +/- 0.007 ml/mm Hg per kg (p less than 0.01). At the end of the 2 hour infusion, arterial pressure increased and was now unchanged from control. Central blood volume had returned to baseline, 17.8 +/- 0.9 ml/kg. Total blood volume and unstressed vascular volume remained unchanged. With the long-term infusion, both arterial and venous compliance decreased (p less than 0.02) to 0.050 +/- 0.006 and 1.50 +/- 0.06 ml/mm Hg per kg, respectively, such that neither value was different from control. Nitroglycerin levels remained constant throughout.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of cardiac function and venous return in thyrotoxic calves.

The mechanisms responsible for maintenance of the high-output state associated with thyrotoxicosis have been investigated by measurement of cardiac-function curves and venous compliance during ganglionic blockade with trimethaphan. Thirteen calves were injected daily with L-thyroxine (200 micrograms/kg) for 12-14 days. Thyroxine treatment increased heart rate (70%), left ventricular systolic pressure (22%), cardiac output (120%), left ventricular maximum rate of pressure development (dP/dt) (56%), and total blood volume (18%) and decreased systemic vascular resistance (39%). These hemodynamic changes persisted during ganglionic blockade or autonomic blockade with atropine and propranolol. Cardiac-function curves in conscious thyrotoxic calves were displaced upward and to the left. Mean circulatory filling pressure (MCFP), measured during anesthesia, was increased from 8 +/- 1 to 12 +/- 1 mmHg. During autonomic and ganglionic blockade MCFP remained elevated after treatment with thyroxine. Venous compliance decreased from 2.1 +/- 0.2 to 1.3 +/- 0.1 ml X mmHg-1 X kg-1 after thyroxine. Unstressed vascular volume was increased from 52.3 +/- 1.1 to 67.1 +/- 0.9 ml/kg. Thus the elevated cardiac output and new cardiac-function curve in thyrotoxicosis are associated with a combination of increased inotropic state, increased blood volume, and decreased venous compliance. These effects are not the result of autonomic influences and may represent direct actions of thyroid hormone on the heart and peripheral venous circulation.