Changes in the proportion of A- and B-types of granules containing atrial and brain natriuretic peptides in atrial myocytes in vasorenal hypertension in rats

The system of cardiac natriuretic peptides (NP) is a very important factor opposing the effects of the rennin-angiotensin-aldosterone system (RAAS), sympathoadrenal system and vasopressin to reduce blood pressure. In the present study, we analyzed the release of atrial and brain natriuretic peptides in the myocytes of the right atrium in rats by the quantitative morphometric method using double immunocytochemical labeling of atrial granules comprising NP in vasorenal hypertension induced by the renal artery ligation. The decrease in the total amount of secretory granules in atrium myocytes by 18% was detected on the 30th day after the operation. The number of the A-type granules was reduced by 53%, and the number of B-type granules was increased by 64% in comparison with the intact animals. Our data indicate activation of NP secretion in vasorenal hypertension. The results suggest that high arterial pressure might be explained by reduced expression of NP receptors in this pathology.     

Central hemodynamics of dogs in the early postresuscitation period and the outcome of resuscitation

Variations in central hemodynamics of dogs were compared with the outcome of resuscitation of 18 dogs subjected to 12-minute reversible circulatory arrest because of ventricular fibrillation. Nine survived dogs with completely recovered neurological status during the first 10 minutes after resuscitation had moderate hypertension, the mean arterial pressure (MAP) being 175.0 + 8.9 mm Hg. In the dogs who died within 24-48 hours after resuscitation, the MAP did not rise during this period as compared to the initial level; 2 dogs developed excessive hypertension (MAP about 200 mm Hg). There were also found certain differences in other parameters of central hemodynamics. Moderate hypertension in the first 10 minutes of the postresuscitation period leads to rapid restoration of the adequate level of peripheral blood flow in organs and tissues, thus favouring survival of animals subjected to a long circulatory arrest.     

Effects of embolus size on hemodynamics and gas exchange in canine embolic pulmonary hypertension

We examined the effects of different-sized glass-bead embolization on pulmonary hemodynamics and gas exchange in 12 intact anesthetized dogs. Pulmonary hemodynamics were evaluated by multipoint pulmonary arterial pressure (Ppa)/cardiac output (Q) plots before and 60 min after sufficient amounts of 100-microns (n = 6 dogs) or 1,000-microns (n = 6 dogs) glass beads to triple baseline Ppa were given and again 20 min after 5 mg/kg hydralazine in all the animals. Gas exchange was assessed using the multiple inert gas elimination technique in each of these experimental conditions. Embolization increased both the extrapolated pressure intercepts (by 6 mmHg) and the slopes (by 5 mmHg.l-1.min.m2) of the linear Ppa/Q plots, together with an 80% angiographic pulmonary vascular obstruction. These changes were not significantly different in the two subgroups of dogs. However, arterial PO2 was most decreased after the 100-microns beads, and arterial PCO2 was most increased after the 1,000-microns beads. Both bead sizes deteriorated the distribution of ventilation (VA)/perfusion (Q) ratios, with development of lung units with higher as well as with lower than normal VA/Q. Only 100-microns beads generated a shunt. Only 1,000-microns beads generated a high VA/Q mode and increased inert gas dead space. Hydralazine increased the shunt and decreased the slope of the Ppa/Q plots after 100-microns beads and had no effect after 1,000-microns beads. We conclude that in embolic pulmonary hypertension, Ppa/Q characteristics are unaffected by embolus size up to 1,000 microns.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of extrahepatic congenital portosystemic shunt morphology in predisposed dog breeds

ABSTRACT: BACKGROUND: An inherited basis for congenital extrahepatic portosystemic shunts (EHPSS) has been demonstrated in several small dog breeds. If in general both portocaval and porto-azygous shunts occur in breeds predisposed to portosystemic shunts then this could indicate a common genetic background. This study was performed to determine the distribution of extrahepatic portocaval and porto-azygous shunts in purebred dog populations. RESULTS: Data of 135 client owned dogs diagnosed with EHPSS at the Faculty of Veterinary Medicine of Utrecht University from 2001 - 2010 were retrospectively analyzed. The correlation between shunt localization, sex, age, dog size and breed were studied. The study group consisted of 54 males and 81 females from 24 breeds. Twenty-five percent of dogs had porto-azygous shunts and 75 % had portocaval shunts. Of the dogs with porto-azygous shunts only 27 % was male (P = 0.006). No significant sex difference was detected in dogs with a portocaval shunt. Both phenotypes were present in almost all breeds represented with more than six cases. Small dogs are mostly diagnosed with portocaval shunts (79 %) whereas both types are detected. The age at diagnosis in dogs with porto-azygous shunts was significantly higher than that of dogs with portocaval shunts (P < 0.001). CONCLUSION: The remarkable similarity of phenotypic variation in many dog breeds may indicate common underlying genes responsible for EHPSS across breeds. The subtype of EHPSS could be determined by a minor genetic component or modulating factors during embryonic development.     

Renal angiography and age in various cardiovascular diseases (morphometric analysis)

Two hundred and fifty-eight angiograms have been analysed, 78 of them are from persons without any renal and cardio-vascular pathology, 184--from patients with vasorenal hypertension. Total area of transversal sections of the arteries is stated (characterizing the arterial bed capacity of the kidney) and its relation to the transversal section area of the renal projection (arterio-renal index). These parameters decrease with age, and are especially noticeable when vasorenal hypertension is present. Stenosis of renal arteries (up to 30%) of various etiology do not practically change the capacity of the renal arterial bed, and when the degree of stenosis increases up to 80%, an essential decrease both in the arterial bed capacity and in the arterio-renal index takes place.     

Renal artery aneurysms in children]

Renal artery aneurysms were diagnosed in 11 patients (9 boys) aged 1 to 14. The examinations were carried out for vasorenal hypertension in 4 cases, for bladder-ureter reflux, hematuria, nephroptosis in 4, ureterohydronephrosis in 2 cases, and for interstitial nephritis. Aneurysms of the major trunk of the renal artery, mostly oval-shaped, 11 x 14 to 25 x 28 mm in size, were detected in 4 patients, intrarenal aneurysms 2 x 3 to 5 x 6 mm in size in 7 cases. The share of aneurysms among uronephrologic conditions in children was found to be 1.54%, among vasorenal hypertension cases, 4.3%. Vasorenal hypertension is the main optional sign of aneurysms of the main trunk of the renal artery, whereas for intrarenal aneurysms such sign is hematuria.     

The use of Doppler ultrasound of the renal arteries for the diagnosis of vasorenal hypertension at the outpatient stage]

Ultrasonic dopplerography of the renal arteries was used to improve the differential diagnosis of arterial hypertension before hospitalization. Dopplerograms of the renal arteries of normal subjects were characterized by almost symmetrical parameters of the blood stream. In patients with vasorenal hypertension a marked asymmetry of the blood stream was seen with its reduction and qualitative changes in the dopplerogram on the side of the stenosed renal artery, that was confirmed by angiographic findings. Chronic pyelonephritis was dopplerographically characterized by hemodynamically insignificant asymmetry of the blood stream in the renal arteries with its reduction on the side of the involved kidney. In essential hypertension the type of asymmetry of blood stream parameters in the renal artery seemed similar to that in normal subjects.     

Experimental assessment of the effectiveness of modified polyhemoglobin in the model of extreme hemodilution

The efficacy of the modified polyhemoglobin suggested as an artificial oxygen transporting substitute was estimated in the model of extreme hemodilution in dogs. It was shown that O2 consumption in dogs had been supported on the normal level during 4 hours after total exchange transfusion with the polyhemoglobin solution. Index of hemodynamics testifies that preparation has hemodynamics action. The conclusion was made that this modified polyhemoglobin has been effective O2 carrying blood substitute.     

Diagnostic possibilities of contrast magnetic resonance tomography

The practice of examinations of more than 400 patients in the diagnostic center of CRIRR showed a high diagnostic efficiency of contrast MRA, especially in stenoses, occlusions, pathologic bends of the brachiocephalic vessels; aneurysms and stenoses of the abdominal and thoracic aorta, stenoses and occlusions of visceral branches of the abdominal aorta, iliac arteries including condition of vessels after surgical correction. Valuable facts have been obtained in vasorenal hypertension caused by stenoses, occlusions, extravasal compressions, additional arteries, and in the portal system (thrombosis of the main trunk and branches of the portal vein, signs of portal hypertension).     

Circulating neuropeptide Y does not produce pulmonary hypertension during massive sympathetic activation.

We tested the possibility that neuropeptide Y (NPY) may contribute to the pulmonary hypertension that occurs after massive sympathetic activation produced by intracisternal veratrine administration in the chloralose-anesthetized dog. In six dogs, veratrine caused arterial NPY-like immunoreactivity (NPY-LI) to rise from 873 +/- 150 (SE) pg/ml to peak values of 3,780 +/- 666 pg/ml by 60-120 min. (In 3 animals, adrenalectomy significantly reduced the increases in NPY-LI.) In five additional dogs, we infused porcine NPY for 30 min in doses that increased arterial NPY-LI to 8,354 +/- 1,514 pg/ml and observed only minor changes in pulmonary hemodynamics. In three isolated perfused canine left lower lung lobe (LLL) preparations, increasing doses of NPY were administered, producing levels of plasma NPY-LI, at the highest dose, that exceeded those observed after veratrine administration by three orders of magnitude. No changes in LLL arterial or double-occlusion capillary pressures were observed at any dose. Similarly, no changes in LLL hemodynamics were observed in three additional lobes when NPY was administered while norepinephrine was being infused. We conclude that it is unlikely that NPY plays a role as a circulating vasoactive agent in producing the pulmonary hypertension and edema that occur in this model.     

Condition of the capillary circulation of gastrointestinal organs after decompression of the portal system by splenorenal anastomosis

The hemomicrocirculatory bed of the gastrointestinal tract organs has been studied in 12 mongrel dogs in 5, 10, 30 days after formation of decompressive splenorenal anastomosis. The most favourable effect the anastomosis renders on hemodynamics in the stomach and duodenal vessels. In these organs during 10 days after the operation phenomena of venous congestion are eliminated, hemorrhages, existed at portal hypertension, resolve, regeneration in the microvessel walls is noted. In the jejunum the restorative processes are slower and complete only 1 month after the operation. The data obtained on the state of the hemomicrocirculatory bed are proved by means of morphometrical investigations.     

Compensatory and adaptive changes in the heart after pulmonary resection (morphometric analysis)

The experiment has been performed in 124 non-inbred dogs by means of a complex of morphometrical methods in order to study compensatory-adaptive processes in the heart after pulmonary resection various in its volume. After 58% resection, and especially after 67-75% resection of the lung mass, a stable pulmonary arterial hypertension appears; it results in development of a chronic cor pulmonale and terminates in its decompensation. Application of extrapulmonary arterio-venous anastomosis, before 67-75% of the pulmonary parenchyma is resected, decreases hypertension in the pulmonary circulation, improves adaptive changes of the heart in the newly formed conditions of hemodynamics, preventing development of its failure.     

Evaluation of the Microcirculation in Chronic Thromboembolic Pulmonary Hypertension Patients: The Impact of Pulmonary Arterial Remodeling on Postoperative and Follow-Up Pulmonary Arterial Pressure and Vascular Resistance

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is generally recognized to be caused by persistent organized thrombi that occlude the pulmonary arteries. The aim of this study was to investigate the characteristics of small vessel remodeling and its impact on the hemodynamics in CTEPH patients.ConclusionThe vascular remodeling of the pulmonary muscular arteries was closely associated with the hemodynamics of CTEPH. Severe pulmonary arteriopathy might be related to residual pulmonary hypertension after PEA. Those altered pulmonary arteries might be a new target for the persistent PH after the operation.     

Radiologic endovascular prosthesis of the renal arteries in patients with renovascular hypertension]

A high percentage of restenoses after roentgenovascular dilatation of the renal arteries laid the basis of a search for new therapeutic methods for these patients. Experiments on implantation of nitinol spiral endoprostheses showed their ability for long-term permeability of renal arteries, not causing their thrombosis and intimal spreading, destruction of formed elements of the blood, change in plasma proteins. Morphological investigations have shown rapid formation (during 14 days) of connective tissue neointima, covered on the side of the blood flow with the true vascular endothelium (ensuring a nonadhesive surface and laminar blood flow), around the coils of an endoprosthesis. This method after its experimental development started to be used in clinical practice. The authors reported the first experience in the clinical use of this method (12 patients with vasorenal hypertension). A 15-month follow-up revealed a stable antihypertensive effect in all patients.     

Pulmonary vasoconstriction in a canine model of neurogenic pulmonary edema

The intracisternal administration of veratrine to the chloralose-anesthetized dog produces pulmonary hypertension (PH) and neurogenic pulmonary edema (NPE). To determine whether pulmonary vasoconstriction, mediated by a circulating agent, contributes to the PH, the left lower lung lobe (LLL) perfusion of seven splenectomized (to keep hematocrit and blood viscosity constant) dogs was isolated so the LLL could be perfused at constant flow and outflow pressure with blood pumped from the pulmonary artery. The LLL was denervated by removing it from the dog. Veratrine (40-160 micrograms/kg) increased LLL arterial pressure by 39.2% and produced large increases in plasma catecholamine concentrations. The double-occlusion technique indicated that 74% of the increase in the LLL arteriovenous pressure gradient was due to an increase in venous tone. This pattern of vasoconstriction was similar to that previously observed during the infusion of exogenous catecholamines and suggested that catecholamines mediated the LLL response. The more severe degree of PH observed in the intact animal in NPE, however, suggests that passive rather than active changes in pulmonary hemodynamics are predominantly responsible for the development of PH in this disorder.     

Characteristics of the reconstruction of collateral pathways after surgical decompression of the portal system

In 20 mongrel dogs after a preliminary stenosis of the portal vein, formation of the spleno-renal or mesenteric-caval anastomosis has been performed. For revealing the vessels vital portography, injection of roentgenopaque masses and morphometry have been carried out. The spleno-renal anastomosis ensures a selective outflow of blood from the esophago-gastro-splenic zone. The collaterals, developing as a result of the porto-caval anastomoses with the anterior vena cava, and the collaterals, developing as a results of the porto-portal anastomoses, disappear. The mesenteric-caval anastomoses favourably affects the intestinal hemodynamics. The bypasses of the blood stream, developed between the portal vein and posterior vena cava reduce predominantly. The decompressive angioanastomoses result in local hypertension in the posterior vena cava system.     

Reversal of reflex pulmonary vasoconstriction induced by main pulmonary arterial distension

Distension of the main pulmonary artery (MPA) induces pulmonary hypertension, most probably by neurogenic reflex pulmonary vasoconstriction, although constriction of the pulmonary vessels has not actually been demonstrated. In previous studies in dogs with increased pulmonary vascular resistance produced by airway hypoxia, exogenous arachidonic acid has led to the production of pulmonary vasodilator prostaglandins. Hence, in the present study, we investigated the effect of arachidonic acid in seven intact anesthetized dogs after pulmonary vascular resistance was increased by MPA distention. After steady-state pulmonary hypertension was established, arachidonic acid (1.0 mg/min) was infused into the right ventricle for 16 min; 15-20 min later a 16-mg bolus of arachidonic acid was injected. MPA distension was maintained throughout the study. Although the infusion of arachidonic acid significantly lowered the elevated pulmonary vascular resistance induced by MPA distension, the pulmonary vascular resistance returned to control levels only after the bolus injection of arachidonic acid. Notably, the bolus injection caused a biphasic response which first increased the pulmonary vascular resistance transiently before lowering it to control levels. In dogs with resting levels of pulmonary vascular resistance, administration of arachidonic acid in the same manner did not alter the pulmonary vascular resistance. It is concluded that MPA distension does indeed cause reflex pulmonary vasoconstriction which can be reversed by vasodilator metabolites of arachidonic acid. Even though this reflex may help maintain high pulmonary vascular resistance in the fetus, its function in the adult is obscure.     

Pulmonary hypertensive response to foreign body microemboli

Pulmonary hypertension and foreign body granulomas are recognized sequelae of chronic intravenous drug abuse. We have recently described the development of transient pulmonary hypertension and increased permeability pulmonary edema after the intravenous injection of crushed, suspended pentazocine tablets in both humans and dogs. To determine the role of vasoactive substances in the development of this transient pulmonary hypertension, we measured pulmonary hemodynamics and accumulation of arachidonic acid metabolites in dogs during the infusion of indomethacin, a cyclooxygenase inhibitor, diethylcarbamazine (DEC), a lipoxygenase inhibitor, and FPL 55712, a receptor antagonist for leukotriene C4/D4 (LTC4/D4). Following the intravenous administration of crushed, suspended pentazocine tablets (3-4 mg/kg of body weight), mean pulmonary artery pressure increased from 14 +/- 2 mmHg to 30 +/- 6 mmHg (p less than 0.05) at 60 secs with a concomitant increase in plasma concentrations of 6-keto-PGF1 alpha from 187 +/- 92 pg/ml to 732 +/- 104 pg/ml and thromboxane B2 from 206 +/- 83 pg/ml to 1362 +/- 117 pg/ml (both p less than 0.05). Indomethacin prevented the increase in both cyclooxygenase metabolites, but had no effect on the pulmonary hypertension. In contrast, DEC had no effect on the increase in cyclooxygenase products, but blocked the pulmonary hypertension. FPL 55712 did not effect either the increase in cyclooxygenase metabolites or the pulmonary hypertension. We conclude that the transient pulmonary hypertension, induced by the intravenous injection of crushed, suspended pentazocine tablets, is not mediated by cyclooxygenase products but may be mediated by lipoxygenase product(s) other than LTC4/D4.     

Sinoaortic deafferentation reduces intrapulmonary shunt in dogs with oleic acid lung injury

Hypoxic stimulation of the peripheral chemoreceptors has been reported to inhibit hypoxic pulmonary vasoconstriction. To evaluate the pathophysiological importance of this observation, we investigated the effects of surgical peripheral chemoreceptor denervation on pulmonary vascular tone and gas exchange in 17 pentobarbital-anesthetized dogs with oleic acid pulmonary edema. Pulmonary arterial pressure-cardiac index (Ppa/Q) plots, blood gases, and intrapulmonary shunt measured by the SF6 method were obtained at base line, after peripheral chemodenervation (n = 9) or after sham operation (n = 8), and again after 0.09 ml.kg-1 intravenous oleic acid. Over the range of Q studied (2-5 l.min-1.m-2), Ppa/Q plots were best fitted as first-order polynomials in most dogs in all experimental conditions. Chemoreceptor denervation increased Ppa at the lowest Q, while sham operation did not affect the Ppa/Q plots. Oleic acid increased Ppa over the entire range of Q and increased intrapulmonary shunt. This latter was measured at identical Q during the construction of the Ppa/Q plots. Chemoreceptor-denervated dogs, compared with sham-operated dogs, had the same pulmonary hypertension but lower intrapulmonary shunt (36 +/- 4 vs. 48 +/- 5%, means +/- SE, P less than 0.04) and venous admixture (43 +/- 4 vs. 54 +/- 3%, P less than 0.02). We conclude that in intact dogs chemoreceptor denervation attenuates the rise in intrapulmonary shunt after oleic acid lung injury. Whether this improvement in gas exchange is related to an enhanced hypoxic pulmonary vasoconstriction is uncertain.     

Effects of gonadectomy on prolactin and LH secretion and the pituitary-thyroid axis in male dogs

The effects of gonadectomy on the secretion of prolactin, LH, TSH, and thyroxine were investigated. Blood serum hormone concentrations were analysed before and at 20, 120, and 180 min after a single iv TRH injection in each of eight healthy intact and castrated male beagle dogs before (control) and after 4-week treatment with the dopamine-2 receptor agonist cabergoline. Under control conditions the mean prolactin, TSH, and thyroxine concentrations were similar in intact and gonadectomised dogs, and administration of TRH provoked a significant (p < 0.01) increase in concentrations of the three hormones. The overall inhibitory effect of cabergoline treatment on prolactin secretion was more pronounced in the castrated dogs compared with the intact group. Cabergoline significantly suppressed the TRH-induced prolactin increase in each group (p < 0.01). Corresponding TRH-stimulated TSH concentrations were not affected by cabergoline. In the gonadectomised dogs, thyroxine concentrations before and at 120 and 180 min after TRH injection were significantly lower than under control conditions. LH concentrations were always higher (p < 0.01) in gonadectomised dogs compared with the intact dogs, but appeared to be affected neither by TRH nor by cabergoline administration. It can thus be concluded from the results, that gonadectomy does not result in hyperprolactinaemia in male dogs, while LH concentrations are significantly increased due to missing androgen feedback. Thyroid function remains unaffected by gonadectomy. Testicular steroids appear to interact with central dopaminergic and probably other neuroendocrine mechanisms regulating the secretion of prolactin, TSH, and thyroxine. Thus, long-term dopamine-2 receptor agonistic treatment may lead to a hypothyroid condition in castrated male dogs.