Length-tension properties of the anterior tibial artery in normotensive and perinephritic hypertensive dogs

The length-active tension relation has been previously reported to be decreased or unchanged in hypertensive vessels whereas resting distensibility was unchanged or increased. We found the maximum active stress and the internal ring circumference, in millimeters, at which it occurs (Lmax) to be lower in arterial rings from perinephritic hypertensive dogs than in rings from normotensive dogs. The internal circumferences (length) at which resting force and active force became zero (L0 and Lmin, respectively) were unchanged. Lmax, L0 and Lmin were used to normalize length-tension diagrams. Active stress was significantly lower in hypertensive vessels at most of the lengths tested with the diagram normalized to Lmax. When the length-tension diagram was normalized to Lmin there was no difference in the active stress at any of the lengths tested. The length-resting stress curves were identical when rhe diagram was normalized to Lmax but the curve for hypertensive vessels was higher when the diagram was normalized to L0. An important characteristic of these length-tension curves is that normalized lengths correspond to the same absolute length in each group of vessels when the reference length has the same absolute value (L0 and Lmin in this study). This separates differences due to absolute length from differences associated with hypertension. We conclude that perinephritic hypertension in the dog is accompanied by a decrease in resting distensibility of the arterial wall. The results indicate that the choice of reference length may affect the values of stress and tension that are obtained for comparison of length-tension relationships in hypertensive and normotensive blood vessels.     

Plasma marinobufagenin-like and ouabain-like immunoreactivity during saline volume expansion in anesthetized dogs

OBJECTIVES: This study investigated effects of acute plasma volume expansion on plasma levels and urinary output of two endogenous Na,K-ATPase inhibitors, marinobufagenin-like and ouabain-like immunoreactive substances. METHODS: Plasma volume was expanded for 3 h via intravenous saline infusion in three groups of anesthetized dogs--nontreated (n = 5); pretreated with rabbit antidigoxin (n = 5); and pretreated with rabbit antimouse (control) antibody (n = 4). RESULTS: Plasma marinobufagenin-like immunoreactivity increased to 11.87 +/- 3.16 nmol.l-1 (vs. 0.30 +/- 0.16 nmol.l-1) within 10 min of volume expansion, in parallel with a 15% increase in LVdP/dt, then decreased to 2.21 +/- 0.59 nmol.l-1, and in 90 min increased to 11.8 +/- 2.8 nmol.l-1, in parallel with the maximal natriuretic response. Plasma concentrations of ouabain-like immunoreactive material were increased after 90 min of saline infusion (0.019 +/- 0.004 nmol.l-1 vs. 0.139 +/- 0.056 nmol.l-1). Pretreatment of the animals with antidigoxin antibody blocked the positive inotropic and reduced natriuretic response to volume expansion, and decreased the urinary release of marinobufagenin-like, but not ouabain-like, material. CONCLUSIONS: These results show the presence of marinobufagenin-like immunoreactive substance in dog plasma and suggest that mammalian EDLF may have a bufodienolide nature. Endogenous marinobufagenin-like immunoreactive substance, which is likely to cross-react with antidigoxin antibody, is involved in the natriuretic and positive inotropic responses to plasma volume expansion.     

Partition of carotid sinus baroreceptor response in dogs with chronic renal hypertension

This study was designed to determine whether resetting of the carotid sinus baroreceptors in chronic renal hypertension is due to altered distensibility of the wall, or changes in the properties of the receptor elements, or both. Dogs were made hypertensive by 50% constriction of the left renal artery with a Goldblatt clamp and by right nephrectomy one week later. Five to nine weeks after nephrectomy, when mean blood pressure had risen by 35-46 mm Hg, the isolated carotid sinus wall deformation, measured from still photographs, and gross baroreceptor nerve action potentials (N) were recorded in response to step intrasinus pressure forcings (P), ranging from zero to 300 mm Hg, in increments of 25 mm Hg. Measured wall deformation was converted to strain-energy density (SED), a scalar value, as the best indicator of the mechanical state of the sinus wall. Plots of N vs. P data followed an S-shaped pattern, but were shifted toward the P-axis, as compared to controls. Plots of SED vs. P, though linear over most of the pressure range, were shifted toward the SED-axis, as compared to controls. A plot of N vs. SED, derived from the composite plots of N vs. P and SED vs. P, followed an S-shaped pattern and also was shifted toward the SED-axis. We conclude that the nonlinearity in the N vs. P curve is due largely to the inability of the receptor elements to respond to increasing wall strain and to resetting of the baroreceptors due to changes in the receptor properties rather than in the wall elements.     

Development of pulmonary hypertension after lung volume reduction surgery

This prospective, longitudinal study was designed to assess the hemodynamic changes occurring in patients who undergo lung volume reduction surgery (LVRS). Patients with emphysema treated with LVRS underwent hemodynamic evaluation before and after surgery. The study group consisted of nine patients with an average age of 64.4 yr. FEV1 rose significantly from 0.64 preoperatively to 0.99 L postoperatively. After surgery, pulmonary artery (PA) systolic pressure rose to 47.9 +/- 12.4 mm Hg, meeting criteria for development of pulmonary hypertension. In six patients, the elevation in PA pressure was attributed to an increase in the pulmonary vascular resistance, but for all nine patients the change was not statistically significant. The pulmonary artery occulsion pressure (PAOP) did not change postoperatively. There was no correlation of PAOP with global left ventricular ejection fraction. While preoperatively there was a negative correlation between symptoms (Mahler dyspnea index) and PA pressure, after surgery the change in PA pressures did not correlate with the change in symptoms (Mahler transitional dyspnea index). We concluded that development of pulmonary hypertension may occur after LVRS in patients whose symptomatic status improves and in whom this condition was not present preoperatively.     

Iso-oncotic volume expansion in the nephrotic syndrome

1. In previous studies we found that albumin infusions caused only a modest natriuresis in the nephrotic syndrome, suggesting that hypovolaemia played no part in the sodium retention of these patients. However, this finding was inconclusive, since the hyperoncocity of the infused albumin probably opposed sodium excretion. 2. In the present study, we examined the effect of sustained (68 h) plasma volume expansion (+18%), by means of iso-oncotic albumin infusions, on renal function, blood pressure, humoral factors and sodium balance. 3. Plasma atrial natriuretic peptide levels increased almost threefold and renin-angiotensin system activity was suppressed. Glomerular filtration rate remained unchanged, whereas estimated renal plasma flow increased, resulting in a further decrease in filtration fraction. 4. The increase in plasma volume expansion was accompanied by a modest increase in sodium excretion, which, however, was less than the amount of sodium daily infused with the albumin solutions and consumed with the diet, so that net sodium was retained. 5. This observation supports the concept that an intrinsic renal defect causes the sodium retention in the nephrotic syndrome, and argues against the therapeutic use of albumin infusions.     

The volume expansion accompanying the martensite transformation in iron-carbon alloys

A dilatometric investigation was conducted to determine the effect of carbon on the volume expansion accompanying the martensite transformation in iron-carbon alloys. It was found that the volume expansion at theM _s temperature varies from 2.0 pct at 0.19 wt pct carbon to 3.1 pet at 1.01 pct carbon, largely due to the effect of carbon on lowering the temperature at which the transformation occurs. Also of importance is the solid solution effect of carbon on altering the lattice parameters of both the austenite and martensite phases at theM_s.     

The volume expansion accompanying the martensite transformation in iron-carbon alloys

A dilatometric investigation was conducted to determine the effect of carbon on the volume expansion accompanying the martensite transformation in iron-carbon alloys. It was found that the volume expansion at theM _s temperature varies from 2.0 pct at 0.19 wt pct carbon to 3.1 pet at 1.01 pct carbon, largely due to the effect of carbon on lowering the temperature at which the transformation occurs. Also of importance is the solid solution effect of carbon on altering the lattice parameters of both the austenite and martensite phases at theM_s.     

Pathways regulating cardiovascular changes during volume loading in awake dogs

The role played by the cardiac sympathetic nerves and arterial baroreceptors in the cardiovascular responses to acute volume loading was studied in conscious dogs. In 15 normally innervated animals, mean arterial pressure rose 10 mmHg, heart rate increased 38 beats/min and cardiac output 1,696 ml/min, while peripheral resistance decreased 0.99 PRU. Neither bilateral baroreceptor denervation, dorsal root sections (T1-T5) or surgical interruption of the left ansa subclavia altered the above responses to acute volume loading. Bilateral section of the ansa subclavia (total cardiac sympathectomy) significantly reduced the heart rate response from 35 +/- 5 to 20 +/- 5 beats/min but did not alter other changes. A similar reduction in heart rate response was observed following selective section of the right ansa subclavia. Intravenous infusions of epinephrine augmented the heart rate response in both normally innervated and cardiac sympathectomized dogs. It is suggested that although the primary efferent pathway for the reflex trachycardia is via the vagus, responses are modulated by sympathetic neural activity. Additionally, the nervous system was not shown to play a measureable role in the observed peripheral resistance changes.     

Renal sodium reabsorption following induction of recovery from volume expansion

In the rat, infusion of a volume of isotonic saline equal to 2% of body weight resulted in an 82% increase in delivery of filtrate out of the proximal tubule but little or, in some animals, no change in the urinary excretion of sodium. By contrast, further degrees of volume expansion resulted in lesser increases in the distal delivery of filtrate, but were associated with a marked increase in the urinary excretion of sodium. Sixty minutes following completion of volume expansion, while the animals were still in positive sosium balance, the urinary excretion of sodium decreased 52% compared to a decrease of only 24% in the distal delivery of filtrate. During the course of progressive volume expansion and during the recovery phase, there was a dissociation between alterations in sodium reabosrption in the proximal convoluted tubule and in the whole kidney. These studies indicate that although the proximal tubule is more sensitive to changes in the extracellular fluid volume, distal nephron sites are ultimately responsible both for the natriuresis of volume expansion and the relative antinatriuresis of the recovery periods.     

Quantification and predictors of plasma volume expansion from mannitol treatment

OBJECTIVE: To determine the effects of acute hypertonic mannitol infusion on intravascular volume expansion and to identify potential predictors of hypervolemia. DESIGN: Measurements of plasma volume and volume regulatory hormones were performed in healthy volunteers before and over 90 min after acute infusion of 20% mannitol solution in a therapeutic dose of 0.5 g/kg body weight, equalling an average infusion volume of 180 ml. SETTING: Clinical research unit in an 800-bed teaching hospital in the eastern part of Switzerland. PARTICIPANTS: Eight normal male volunteers. MEASUREMENTS AND RESULTS: Baseline plasma volume was determined by the indocyanine green dye dilution technique. Serial plasma protein measurements were performed after mannitol infusion to calculate intravascular volume changes. Mannitol administration resulted in a plasma expansion that persisted for more than 90 min and peaked at 112% of the baseline plasma volume 15 min after infusion. Concomitantly, an increase in systolic blood pressure and a fall in plasma sodium concentration occurred. Pharmacokinetic analyses of mannitol distribution and elimination revealed a close relation between plasma volume expansion and mannitol serum concentrations. While renin activity and aldosterone concentrations were suppressed proportionally to the intravascular volume increase, antidiuretic hormone was increased despite notable volume expansion and hyponatremia. Similarly, a rise in atrial natriuretic peptide was detected. CONCLUSIONS: Therapeutic doses of hypertonic mannitol cause substantial plasma volume expansion, resulting in increased blood pressure. Plasma volume expansion is related to mannitol serum concentrations and mannitol clearance determines the time required to restore normovolemia. ADH and ANP are potentially aggravating factors of mannitol-induced hyponatremia.     

Aqueous humor dynamics in beagle dogs with caffeine-induced ocular hypertension

In order to investigate the possible mechanisms for caffeine-induced ocular hypertension, the intraocular pressure (IOP) and the outflow through the trabecular meshwork were measured in beagle dog eyes after dosing with intravenous caffeine (30 mg/kg) alone or in combination with the topical beta-blocker befunolol [applied as 100 microliters of a 1% (w/v) solution] which inhibits aqueous humor formation in the ciliary body. Intravenous injections of caffeine significantly increased the IOP at 0.25 and 1 hr after a single dose. The ocular hypertension recovered within 2 hr following dosing. Over time, there were no differences in the outflow between the caffeine and control groups. The instillation of befunolol lowered outflow and produced ocular hypotension. The levels of the IOP and outflow in dogs treated with caffeine and befunolol in combination were almost the same as those in dogs treated with befunolol alone. Single-dose and combination-dose studies demonstrate that intravenous caffeine increases the IOP in normal beagle dogs possibly by increasing aqueous humor formation and not by the inhibition of aqueous humor drainage through the trabecular meshwork.     

Right ventricular pathology in chronic pulmonary hypertension

Right ventricular free wall biopsy specimens in 40 patients undergoing surgery for relief of chronic thromboembolic pulmonary hypertension were normal in 5%, disclosed only myocyte hypertrophy in 80%, mild focal fibrosis in 12.5%, and myocarditis in 2.5%. There was no relation between postsurgical functional or hemodynamic outcomes and the presence of focal fibrosis.     

Benign intracranial hypertension in chronic myeloid leukemia

Persistent pulmonary hypertension of the newborn (PPHN) is a challenge for the neonatologist and a common indication for treatment with extracorporeal membrane oxygenation (ECMO) when medical management fails. We observed 132 neonates born between January 1985 and December 1988 with the diagnosis of persistent pulmonary hypertension of the newborn: 73 (55%) met the Bartlett criteria for treatment with ECMO with 80% predicted mortality; 21 (29%) deteriorated despite conventional medical treatment, were thought to be dying, and were sent for ECMO. Among the 52 patients who were medically treated 40 (77%) survived, a marked difference compared with a predicted 20% survival. All ECMO-treated neonates survived. Although conventionally treated infants showed a trend toward less dependence on supplemental oxygen at > 28 days of life, this study failed to detect a significant difference between those two groups. We conclude that mortality was lower for ECMO-treated infants than for those who were medically treated (0 of 21 vs 12 of 52, p < 0.05); mortality for infants with persistent pulmonary hypertension of the newborn who met Bartlett's criteria and were medically treated was lower than published data; and there was no significant difference in oxygen dependence at > 28 days between the survivors who received ECMO and those who received medical therapy.     

Arterial hypertension in patients on chronic hemodialysis

Arterial hypertension is frequent among chronically dialyzed patients. The kidney obviously plays a major role in arterial blood pressure control. There is a large number of experimental data emphasizing different factors (in addition to renin important in renal hypertension prognosis) such as: sodium balance, angiotensin, etc [1-8]. Sympathetic activity disorders or lack of vasodilatory prostaglandins and quinine may also play a certain role. In uremic patients peripheral arteriolar resistance is increased, unlike normotensive uremic patients or those who prove to be normotensive upon clinical examinations [8, 11-15]. Hypertension occurs in approximately 80% of patients with chronic renal failure, producing a number of complications primarily affecting the CNS and systemic circulation [5-8, 10, 11, 13]. The study concerned patients on chronic dialysis, with a male to female ratio of 69.9%:32.1%. In most of them the underlying disease, which caused chronic renal failure, was glomerulonephritis (60.0%), then pyelonephritis (17.0%) and nephrosclerosis, nephrolithiasis, polycystic kidney and, finally, renal tumours. The effect of permanent haemodialysis during the first year of treatment, was efficacious on hypertension in 1704 (65.1%) patients; in 672 (25.7%) patients therapeutical effects were achieved by dialysis and antihypertensive drugs, while in 240 (9.2%) subjects there was no improvement. General observations suggest that two types of arterial hypertension persisted in patients with chronic renal failure: volume-dependent arterial hypertension which is more frequent (90-95%) among haemodialyzed patients and renin-dependent hypertension. Such findings are of utmost importance indicating that hypervolaemia is one of the major factors in the development of arterial hypertension in patients with chronic renal failure, with renin playing the secondary role. Salt-free diet should be used in the treatment of arterial hypertension for years, a well conducted haemodialysis is highly effective in the control of arterial hypertension among these patients. In our series of patients dialysed three times a week; normalization of blood pressure was faster with lower incidence of hypertensive crises during haemodialysis and with few complications. Water and sodium excess was reduced by frequent haemodialyses and sudden changes in electrolyte, hydrostatic and other metabolic effects were minimized. Increased values of plasma renin activity were observed in a small number of patients. Ultrafiltration is insufficient for normalization of blood pressure. Hypertensive crises were frequent in these patients. Their response to medicaments such as methyldopa, beta-adrenergic blockers or other antihypertensive drugs, was good. Severe changes in blood vessels, especially in fundus oculi blood vessels were frequent in these patients. The life of hypertensive glomerulonephritis patients was especially endangered (graphs 1-6). In addition to the mentioned factors arterial hypertension during haemodialysis may also be of cardiac origin, including increase in cardiac output due to arteriovenous anastomosis, disequilibrium syndrome, changes in osmotic gradient of both extra- and intracellular spaces with resultant arteriolar wall oedema, erythrocyte amount, hypoxia, composition of dialysis fluid (sodium concentration), plasma osmotic pressure, metabolic acidosis and other factors. More recently, natriuretic hormone has also been indentified as a cause of vascular refraction. Peripherial arteriolar resistance as a cause of arterial hypertension among uremic patients must not be forgotten, because the genesis of arterial hypertension in patients with chronic renal failure is multifactorial. The highest percentage refers to volume-dependent arterial hypertension, whereas the percentage of other aetiologic factors is lower. Haemodialysis enables the normalization of blood pressure in most of hypertensive patients.     

Pulmonary regurgitation in large atrial shunts without pulmonary hypertension

Seven patients with pulmonary regurgitation (PR), normal pulmonary artery (PA) pressures and large left-to-right atrial shunts are reported. Six had secundum atrial septal defects (ASD) and one had anomalous pulmonary venous drainage. These comprised 4% of 180 patients with atrial shunts and normal PA pressures. Pulmonary regurgitation was diagnosed clinically by mid-frequency diastolic decrescendo murmurs beginning after the pulmonic component of the second heart sound, and diagnoses were confirmed by catheterization. In two patients who had serial preoperative catheterizations over 8 and 16 years, PR progressed in one and was present only on the second study in the other. All patients underwent shunt correction, at which time the pulmonic anulus and artery appeared dilated, but the pulmonic valves were normal and did not require revision. In all patients the PR murmur disappeared after shunt correction alone, and on chest X-ray both PA and overall heart size decreased. Although it is known that pulmonary regurgitation occurs with atrial septal defects and pulmonary hypertension, the present study demonstrates that it also occurs with high flow atrial shunts, in which setting it has different implications and is reversible with shunt correction alone.