Myogenic origin of the hypotension induced by rapid changes in posture in awake dogs following autonomic blockade

The "push-pull" effect denotes the reduced tolerance to +G(z) (hypergravity) when +G(z) stress is preceded by exposure to hypogravity, i.e., fractional, zero, or negative G(z). The purpose of this study was to test the hypothesis that an exaggerated, myogenically mediated rise in leg vascular conductance contributes to the push-pull effect, using heart level arterial blood pressure as a measure of G tolerance. The approach was to impose control (30 s of 30 degrees head-up tilt) and push-pull (30 s of 30 degrees head-up tilt immediately preceded by 10 s of -15 degrees head-down tilt) gravitational stress after administration of hexamethonium (5 mg/kg) to inhibit autonomic ganglionic neurotransmission in seven dogs. Cardiac output or thigh level arterial pressure (myogenic stimulus) was maintained constant by computer-controlled ventricular pacing. The animals were sedated with acepromazine and lightly restrained in lateral recumbency on a tilt table. Following the onset of head-up tilt, the magnitude of the fall in heart level arterial pressure from baseline was -11.6 +/- 2.9 and -17.1 +/- 2.2 mmHg for the control and push-pull trials, respectively (P < 0.05), when cardiac output was maintained constant. Over 40% of the exaggerated fall in heart level arterial pressure was attributable to an exaggerated rise in hindlimb vascular conductance (P < 0.05). Maintaining thigh level arterial pressure constant abolished the exaggerated rise in hindlimb blood flow. Thus a push-pull effect largely attributable to a myogenically induced rise in leg vascular conductance occurs when autonomic function is inhibited.     

Influence of vasoactive intestinal polypeptide (VIP) on splanchnic and central hemodynamics in healthy subjects

The influence of VIP, a potent vasodilator, on central hemodynamics, splanchnic blood flow and glucose metabolism was studied in six healthy subjects. Teflon catheters were inserted into an artery, a femoral vein and a right-sided hepatic vein. A Swan-Ganz catheter was introduced percutaneously and its tip placed in the pulmonary artery. Determinations of cardiac output, systemic, pulmonary arterial and hepatic venous pressures as well as splanchnic blood flow were made in the basal state and at the end of two consecutive 45 min periods of VIP infusion at 5 and 10 ng/kg/min, respectively. Arterial blood samples for analysis of glucose, FFA, insulin and glucagon were drawn at timed intervals. VIP infusion at 5 ng/kg/min resulted in an increase in cardiac output (55%) and heart rate (25%) as well as a reduction in mean systemic arterial pressure (15%) and vascular resistance (45%). With the higher rate of VIP infusion heart rate tended to rise further while cardiac output and arterial pressure remained unchanged. At 15 min after the end of VIP infusion the above variables had returned to basal levels. Splanchnic blood flow and free hepatic venous pressure did not change significantly. Arterial concentrations of glucose, FFA, insulin and glucagon increased during VIP infusion. At 15 min after the end of infusion the glucose levels were still significantly higher than basal (20%). Net splanchnic glucose output did not change in response to VIP infusion. It is concluded that VIP exerts a potent vasodilatory effect resulting in augmented cardiac output and lowered systemic blood pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood pressure of sinoaortic-denervated dogs is not increased by cardiac denervation

Although blood pressure rises markedly after acute sinoaortic denervation, animals with chronic sinoaortic denervation have normal or only slightly elevated mean arterial pressures. The present study was performed to determine whether reflexes from cardiac receptors exert antihypertensive effects and thereby lower blood pressure in animals with chronic sinoaortic denervation. We made multiple measurements of blood pressures in dogs with chronic sinoaortic denervation before and after their hearts were denervated surgically. Mean arterial pressure after cardiac denervation (100.3 +/- 4.2 mm Hg) was not significantly different from the mean pressures recorded before cardiac denervation in these sinoaortic-denervated dogs (104.8 +/- 3.1 mm Hg). Also, mean heart rate after cardiac denervation (107.4 +/- 5.5 beats/min) did not differ significantly from the mean heart rate recorded before cardiac denervation (107.2 +/- 5.9 beats/min). Cardiac denervation did, however, appear to reduce the lability of both blood pressure and heart rate in sinoaortic-denervated dogs. We conclude that cardiac receptors are not responsible for maintaining arterial pressure within essentially normal limits in animals with chronic sinoaortic denervation.     

Circulatory effects of prolonged hypoxia before and during antihistamine.

Five chronically instrumented healthy dogs were exposed to a 5-day period of breathing 10% oxygen in a chamber. The response to hypoxia was found to be time dependent. During the first 24 h of hypoxia the circulatory response was characterized by increases in cardiac output, heart rate, pulmonary and systemic arterial blood pressures, and pulmonary vascular resistance. Systemic vascular resistance increased; left atrial pressure decreased. During the early part of hypoxia the animals became hypocapnic; the arterial blood pH rose significantly. During the rest of the hypoxic period cardiac output, heart rate, and arterial blood pH returned to the control values; pulmonary and systemic arterial pressures and pulmonary vascular resistance remained significantly elevated. Systemic vascular resistance rose; left atrial pressure remained below control. This response to hypoxia was not substantially modified when the experiment was repeated during the administration of the antihistamine promethazine, an H1-receptor blocking agent, in a dose which blocked the pulmonary vasoconstrictor response to small doses of exogenous histamine. The circulatory response to acute hypoxia in five anesthetized dogs was not modified by intravenous administration of metiamide, an H2-receptor blocking agent.     

Effect of volume expansion on hemodynamic variables in nephrectomized dogs

We have previously demonstrated that blood pressure elevation by acute blood volume expansion is volume-dependent during the infusion period and resistance-dependent in the post-infusion period in normal anesthetized dogs, and that such an increase in blood pressure is associated with a potentiation of the pressor response to norepinephrine. To evaluate the possible renal contribution to these hemodynamic changes, blood volume expansion was performed for 1 h with dextran dissolved in lactated Ringer's solution (20 ml/kg) in 15 nephrectomized dogs. The mean blood pressure, cardiac output and total peripheral resistance at the end of infusion were 126%, 225% and 60%, respectively; 3 h after volume expansion they were 126%, 151%, and 92% respectively. However, in 4 dogs, there was an increase in mean blood pressure (138%) 3 h after volume expansion. This was thought to result from an increase in the total peripheral resistance (133%) associated with the recovery of cardiac output (106%). The pressor response to norepinephrine (0.5 microgram/kg) was potentiated after volume expansion. These results indicate that the handling of volume by the kidney contributed to the maintenance of an elevated level of cardiac output. However, nephrectomy did not seem to interfere with the hemodynamic switching of the causative factor for blood pressure elevation from increased cardiac output to increased total peripheral resistance. Neither was the potentiation of pressor response to norepinephrine affected.     

Effects of brain renin-angiotensin on cardiovascular function and saline intake in awake dogs

Initial studies were undertaken to investigate the effects of prolonged administration of angiotensin II (AII), 1 micrograms twice daily, via the lateral ventricles to mongrel dogs on arterial blood pressure and to determine if sodium intake was essential for the development of hypertension. Increasing AII levels in the cerebrospinal fluid for a prolonged period of time produced a sustained hypertensive state only in those dogs in which the daily intake of sodium was increased. The hypertension appeared to be due to an increase in total peripheral resistance. Central administration of AII increased both fluid intake and urine output. In order to assess the hemodynamic effects of increasing endogenous brain AII, renin was injected in doses of 0.025, 0.05, 0.1 and 0.3 units (from porcine kidney) into the lateral ventricles of chronically instrumented awake dogs. Hemodynamic variables were recorded prior to and one and 2 h after the central administration of renin. Renin produced a dose-dependent increase in mean arterial pressure with no significant change in heart rate or carotid, coronary and renal blood flow velocities. Chronic intraventricular administration of renin, 0.15 units twice daily to awake instrumented dogs receiving saline as the drinking fluid, markedly increased the daily intake of saline and increased diastolic and systolic blood pressure without increasing heart rate or carotid, coronary or renal blood flow velocities. There appears to be a direct significant relationship between the increase in mean blood pressure due to the intraventricular administration of renin and the volume of saline consumed.     

Changes in systemic hemodynamics following administration of synthetic angiotensin II to dogs of different ages]

Experiments were conducted on dogs aged 18-22 days, 2-3 month-old and adult dogs. Arterial blood pressure, cardiac output, heart rate and total peripheral resistance during the infusion of synthetic angiotensin-II-amide in a dose of 2 mug/kg per minute were studied. An increase of arterial pressure in adult dogs during the action of angiotensin-II was connected with the elevation of the total peripheral resistance. An increase of the total peripheral resistance and also of the cardiac output was seen in the puppies. The differences in the degree of increase of the arterial blood pressure in adult dogs and puppies were not marked.     

Altered baroreflex function after tail suspension in the conscious rat

Experiments were performed on conscious chronically instrumented rats to determine the contribution of peripheral V2-vasopressinergic receptors in any alteration of baroreceptor reflex (BRR) sensitivity on release from 1 wk of 30 degrees head-down tilt resulting from tail suspension. Initial experiments determined changes in plasma volume (PV) occurring over this period by use of the Evans Blue dye dilution technique. PV was determined immediately before tail suspension and on day 7 of the stimulus. PV, erythrocyte volume, and total blood volume were all significantly diminished on day 7, whereas hematocrit was unchanged. Other rats were instrumented with pulsed Doppler flow probes on the ascending aorta for determination of cardiac output and with arterial and venous catheters 7-10 days before study. Immediately before tail suspension, control cardiac output, mean arterial blood pressure, and heart rate values were determined. In addition, BRR sensitivity was estimated both before and after intravenous administration of a V2-receptor antagonist by assessing the slope of the pulse interval-mean arterial blood pressure relationship in response to a series of pressor doses of phenylephrine. BRR sensitivity was determined on the last day of head-down tilt, 1 min after release from tail suspension, and 10 min after administration of a specific V2-vasopressinergic antagonist. BRR sensitivity tended to fall on day 7 of tail suspension compared with control and was significantly increased after release. However, BRR sensitivity was not altered by intravenous V2 antagonist administration either before tail suspension or after release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fructose ingestion acutely elevates blood pressure in healthy young humans

Overconsumption of fructose, particularly in the form of soft drinks, is increasingly recognized as a public health concern. The acute cardiovascular responses to ingesting fructose have not, however, been well-studied in humans. In this randomized crossover study, we compared cardiovascular autonomic regulation after ingesting water and drinks containing either glucose or fructose in 15 healthy volunteers (aged 21-33 yr). The total volume of each drink was 500 ml, and the sugar content 60 g. For 30 min before and 2 h after each drink, we recorded beat-to-beat heart rate, arterial blood pressure, and cardiac output. Energy expenditure was determined on a minute-by-minute basis. Ingesting the fructose drink significantly increased blood pressure, heart rate, and cardiac output but not total peripheral resistance. Glucose ingestion resulted in a significantly greater increase in cardiac output than fructose but no change in blood pressure and a concomitant decrease in total peripheral resistance. Ingesting glucose and fructose, but not water, significantly increased blood pressure variability and decreased cardiovagal baroreflex sensitivity. Energy expenditure increased by a similar amount after glucose and fructose ingestion, but fructose elicited a significantly greater increase in respiratory quotient. These results show that ingestion of glucose and fructose drinks is characterized by specific hemodynamic responses. In particular, fructose ingestion elicits an increase in blood pressure that is probably mediated by an increase in cardiac output without compensatory peripheral vasodilatation.     

Comparison of cardiovascular response to passive tilt in young and elderly men

To test the hypothesis that altered hemodynamic responses to postural changes are associated with aging, cardiovascular responses to head-up tilt (HUT) and head-down tilt (HDT) were examined in 12 healthy young (average age, 24.6 +/- 1.7 years) and 12 healthy elderly (average age, 68.6 +/- 2.2 years) men. Subjects were passively tilted from supine to 30 degrees, 60 degrees, and 90 degrees HUT and HDT. Responses to these perturbations were determined 5 min after tilting with measures of heart rate (HR), blood pressure (SBP, DBP), and echocardiographically determined left ventricular diameter in systole and diastole (LVIDs, LVIDd). In HUT there were no significant age effects. In both young and elderly, SBP decreased significantly (p less than 0.05), and DBP and HR increased significantly. Ejection fraction (EF), mean arterial blood pressure (MABP), and rate-pressure product (RPP) were unchanged in both groups. In HDT, the hemodynamic responses of the young and elderly were in opposite directions and significant age effects were found for SBP, DBP, HR, LVIDs, EF, MABP, and RPP. In HDT, the young appear to increase cardiac output primarily due to an increase in EF and end-diastolic volume (LVIDd), while HR is unchanged and SBP is decreased. MABP is unchanged, suggesting a small decrease in total peripheral resistance. The elderly may increase cardiac output slightly, owing to an increase in LVIDd with no change in EF, and a large increase in HR. Afterload increased markedly, therefore attenuating any increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of citidoline on hemodynamics in the normobaric hypoxic dog]

In dogs submitted to a normobaric hypoxia, we found an elevation of the arterial blood pressure, of the heart rate, of the cardiac output and of the regional blood flows, the total peripheral resistance remaining unchanged. Treatment with citidoline abolishes these hemodynamic responses and the authors hypothetize that this effect is correlated with the agonist dopaminergic effect of the drug.     

Hemodynamic adjustments to head-up posture in the partly arboreal snake, Elaphe obsoleta

Radioactively-labeled microspheres were used to quantify adjustments of regional blood flows in 15 snakes (Elaphe obsoleta) subjected to 45 degrees head-up tilt. Heart rate and peripheral vascular resistance increased during tilt to compensate for the passive drop of pressure at the head. Two snakes failed to regulate blood pressure, but in 13 others arterial pressure increased at midbody (where passive changes in pressure are unexpected due to tilt alone) and arterial pressure at the head averaged 67% of the pretilt value. Tissue blood flow was reduced significantly in visceral organs, posterior skin and posterior skeletal muscle, but was maintained at pretilt levels in brain, heart, lung and anterior tissues. Ventricular systemic output averaged 24 ml/min X kg in horizontal posture and 9.4 ml/min X kg during tilt. Comparable values for pulmonary output were 4 and 6.5 ml/min X kg. Patterns of intraventricular shunting of blood acted to maintain pulmonary flow during tilt. A large right-to-left shunt (mean 76%) was present in horizontal snakes, but the shunted fraction declined during tilt (mean 54%). Left-to-right shunt increased during tilt from 7% to 14%.     

Chemical activation of thin-fiber phrenic afferents. 2. Cardiovascular responses

To assess the effects of groups III and IV (thin-fiber) phrenic afferents on arterial pressure, heart rate, and distribution of cardiac output, we injected capsaicin into phrenic arteries of in situ isolated and innervated left diaphragms of dogs anesthetized with chloralose, vagotomized, and mechanically ventilated. Blood flow in the ascending aorta, common carotid, renal, superior mesenteric, and femoral arteries was measured by electromagnetic and Doppler flow probes. Injection of 1 mg capsaicin into the left phrenic artery produced congruent to 15% increase in mean arterial pressure and congruent to 7% increase in heart rate with no change in aortic flow. Phrenic arterial flow decreased by 64%, renal arterial flow by 16%, and superior mesenteric arterial flow by 10%, whereas carotid flow increased by 13% and flow to the right gastrocnemius muscle did not change. Mean arterial pressure, heart rate, and blood flow distribution (with the exception of the decline in phrenic blood flow) returned to baseline within 60 s of the injection. Injection of 1.5 mg capsaicin into the right isolated and innervated gastrocnemius produced congruent to 35% increase in mean arterial pressure, 17% rise in heart rate, and no change in aortic blood flow. Phrenic and carotid arterial flow rose by 240 and 41%, respectively, whereas renal and superior mesenteric flow declined by 50 and 20%, respectively. In conclusion, thin-fiber phrenic afferents have an excitatory effect on arterial pressure and heart rate. They redistribute blood flow away from the renal and intestinal vascular beds and toward the carotid vascular bed. On the other hand, the cardiovascular reflex from thin-fiber phrenic afferents seems less potent than that from limb muscle afferents.     

Effects of pituitary adenylate cyclase-activating polypeptide on cardiovascular and respiratory responses in anaesthetised dogs

This study examines some of the cardiovascular and respiratory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in anaesthetised dogs. Intravenous injection of PACAP 27 caused an increase in arterial blood pressure and an increase in heart rate. The blood pressure response was significantly reduced by adrenoceptor blockade suggesting a mechanism of action mediated in part via catecholamines. The heart rate increase was unaltered by adrenoceptor blockade suggesting a direct effect of PACAP 27. PACAP 27 also caused potentiation of cardiac slowing caused by stimulation of the vagus nerve. In addition, PACAP 27 powerfully stimulated breathing. This was probably evoked by stimulation of arterial chemoreceptors, because bilateral section of the carotid sinus nerves abolished this effect. PACAP 27 had no effect on the ability of the cardiac sympathetic nerve to increase heart rate, nor on the interaction between the sympathetic and parasympathetic systems in the heart.     

Postnatal hemodynamic changes in very-low-birthweight infants.

The purpose of this study was to characterize postnatal changes in regional Doppler blood flow velocity (BFV) and cardiac function of very-low-birthweight infants and to examine factors that might influence these hemodynamic changes. Mean and end-diastolic BFV of the middle cerebral and superior mesenteric arteries, cardiac output, stroke volume, and fractional shortening were measured in 20 infants birthweight 1,002 +/- 173 g, gestational age 28 +/- 2 wk) at 6, 30, and 54 h after birth and before and after feedings on days 7 and 14. Postnatal increases in cerebral BFV, mesenteric BFV, and cardiac output were observed that were not associated with changes in blood pressure, hematocrit, pH, arterial PCO(2), or oxygen saturation. The postnatal pattern of relative vascular resistance (RVR) differed between the cerebral and mesenteric vasculatures. RVR decreased in the middle cerebral but not the superior mesenteric artery. Physiological patency of the ductus arteriosus did not alter postnatal hemodynamic changes. In response to feeding, mesenteric BFV and stroke volume increased, and mesenteric RVR and heart rate decreased. Postprandial responses were not affected by postnatal age or the age at which feeding was initiated. However, the initiation of enteral nutrition before 3 days of life was associated with higher preprandial mesenteric BFV and lower mesenteric RVR than was later initiation of feeding. We conclude that in very-low-birthweight infants over the first week of life 1) systemic, cerebral, and mesenteric hemodynamics exhibit region-specific changes; 2) asymptomatic ductus arteriosus patency and early feedings do not significantly influence these postnatal hemodynamic changes; and 3) cardiac function adapts to increase local mesenteric BFV in response to feedings.     

Alteration of systemic hemodynamics in dogs with adrenal hypertension

Arterial hypertension was reproduced in 20 dogs by suturing the adrenal glands with ligature. Arterial pressure showed a significant fall in 2 weeks; cardiac output diminished, and the general peripheral resistance displayed a sharp elevation. The phasic syndrome of hypodynamia, a reduction of the contractility index, of the volumetric rate of cardiac output, of the cardiac index, and of the rate of increase of the intraventricular pressure pointed to reduction of the myocardial contractility. Three months after the suturing there was an even greater elevation of arterial pressure, and hemodynamic shifts were analogous to the two-week hypertension period.     

Metabolic changes in dogs during anaphylactic shock.

Hemodynamic and metabolic parameters were studied in conscious dogs during anaphylactic shock. Mean arterial blood pressure and cardiac output decreased and heart rate increased during shock. FFA flux and O₂ consumption decreased significantly shortly after the challenging injection. RQ was elevated indicating a shift in metabolite utilization towards carbohydrates.     

Hemodynamic effects of blood loss during a passive response to a stressor in the conscious rabbit

In the conscious rabbit, exposure to an air jet stressor increases arterial pressure, heart rate, and cardiac output. During hemorrhage, air jet exposure extends the blood loss necessary to produce hypotension. It is possible that this enhanced defense of arterial pressure is a general characteristic of stressors. However, some stressors such as oscillation (OSC), although they increase arterial pressure, do not change heart rate or cardiac output. The cardiovascular changes during OSC resemble those seen during freezing behavior. In the present study, our hypothesis was that, unlike air jet, OSC would not affect defense of arterial blood pressure during blood loss. Male New Zealand White rabbits were chronically prepared with arterial and venous catheters and Doppler flow probes. We removed venous blood until mean arterial pressure decreased to 40 mmHg. We repeated the experiment in each rabbit on separate days in the presence and absence (SHAM) of OSC. Compared with SHAM, OSC increased arterial pressure 14 +/- 1 mmHg, central venous pressure 3.3 +/- 0.4 mmHg, and hindquarter blood flow 34 +/- 4% while decreasing mesenteric conductance 32 +/- 3% and not changing heart rate or cardiac output. During normotensive hemorrhage, OSC enhanced hindquarter and renal vasoconstriction. Contrary to our hypothesis, OSC (23.5 +/- 0.6 ml/kg) increased the blood loss necessary to produce hypotension compared with SHAM (16.8 +/- 0.6 ml/kg). In nine rabbits, OSC prevented hypotension even after a blood loss of 27 ml/kg. Thus a stressful stimulus that resulted in cardiovascular changes similar to those seen during freezing behavior enhanced defense of arterial pressure during hemorrhage.     

Diversion of blood flow from noncompliant to compliant vasculature in awake dogs: mechanical impact on right atrial pressure

The distribution of cardiac output between compliant vasculature (e.g., splanchnic organs and skin) and noncompliant vasculature (e.g., skeletal muscle) is proposed to constitute an important determinant of the amount of blood available to the heart (central blood volume and pressure). The aim here was to directly test the hypothesis that diversion of blood flow from a relatively noncompliant vasculature (muscle) to compliant vasculature (splanchnic organs and skin) acts to reduce right atrial pressure. The approach was to inflate an occluder cuff on the terminal aorta for 30 s in one of two modes of ventricular pacing in five awake dogs with atrioventricular block and autonomic blockade. In one trial, cardiac output was maintained constant, meaning cuff inflation caused a portion of terminal aortic flow (a noncompliant circulation) to be diverted to the splanchnic and skin circulations (compliant circulations). In the other trial, arterial pressure was maintained constant, meaning blood flow to these other regions did not change. The response of right atrial pressure (corrected for differences in arterial pressure between the two trials) fit our hypothesis, being lower when blood flow was diverted to compliant regions. We conclude that a small (4% of cardiac output) diversion of blood flow from a noncompliant region to a compliant region reduces right atrial pressure by 0.7 mmHg.     

Decreased cardiac output at the onset of diabetes: renal mechanisms and peripheral vasoconstriction

Recently we reported that hindquarter blood flow, measured 24 h/day, decreased progressively over the first 6 days of type 1 diabetes in rats. That response, coupled with the tendency of mean arterial pressure to increase, suggested a vasoconstrictor response. The purpose of this study was to measure the changes in cardiac output together with the renal hemodynamic and excretory responses to allow integrative determination of whether vasoconstriction likely accompanies the onset of type 1 diabetes. Rats were instrumented with a Transonic flow probe on the ascending aorta and with artery and vein catheters, and cardiac output and mean arterial pressure were measured continuously, 24 h/day, throughout the study. The induction of diabetes, by withdrawing intravenous insulin-replacement therapy in streptozotocin-treated rats, caused a progressive decrease in cardiac output that was 85 +/- 5% of control levels by day 7. This was associated with significant increases in glomerular filtration rate, renal blood flow, and microalbuminuria as well as urinary fluid and sodium losses, with a negative cumulative sodium balance averaging 15.7 +/- 1.6 meq by day 7. Restoring insulin-replacement therapy reversed the renal excretory responses but did not correct the negative sodium balance, yet cardiac output returned rapidly to control values. Increasing sodium intake during the diabetic and recovery periods also did not significantly affect the cardiac output response during any period. These results indicate that cardiac output decreases significantly at the onset of type 1 diabetes without glycemic control, and although volume loss may contribute to this response, there also is a component that is not volume or sodium dependent. We suggest this may be due to vasoconstriction, but to what extent local blood flow autoregulation or active vasoconstriction may have mediated that response is not known.