Cardiocyte nuclear chromatin density correlates with transplanted heart left ventricular mass.

INTRODUCTION: Cardiocyte hypertrophy is accompanied by polyploidy, seen as a decrease in chromatin density in the enlarged nucleus. Repeated biopsies of a transplanted heart offer the possibility of a dynamic evaluation of these phenomena. The aim of this work was an evaluation of cardiocyte nuclear chromatin density in transplanted hearts during long-term follow-up. MATERIALS AND METHODS: The material encompassed myocardial biopsy specimens taken during the first week, first month, and then on an annual basis up to 10 years after surgery. Only biopsy specimens with no rejection were considered (grade "0" International Society for Heart and Lung Transplantation [ISHLT] 122 biopsy specimens). The control group consisted of 7 donor heart specimens. We evaluated the optical density-mean gray level-of cardiomyocyte nuclear chromatin. We determined correlations of this index with the nuclear area, and with left ventricle ultrasound measurements, using correlation analysis. RESULTS: The chromatin mean gray level decreased with time, correlating positively with interventricular septum thickness, left ventricle posterior wall diameter, and left ventricular mass. Analysis of individual periods showed a significant positive correlation of the mean grey level with the cardiocyte nuclear surface in year 3, 4, and 9 after transplantation, thereby suggesting the occurrence of polyploidy at those times. The significant negative correlation of these values (1 week and 1 year) indicated normalization of early cardiocyte hypertrophy. CONCLUSIONS: With the passage of time chromatin condenses, leading to pyknosis. The activity of cardiocyte chromatin correlated with left ventricular hypertrophy. Compensatory cardiomyocyte polyploidy is a periodical phenomenon.

Remodeling of human transplanted myocardium in ten-year follow-up: a clinical pathology study.

UNLABELLED: Remodeling taking place in transplanted myocardium leads to a change in the number of cardiocytes. Ultrasound measurements and biopsy evaluation should reflect their loss and compensation. We sought to evaluate the morphology of the transplanted heart upon long-term follow-up. MATERIAL AND METHODS: Myocardial biopsies were obtained in the first week, first month, and then annually for 10 years from transplantation that did not show rejection (grade "0" ISHLT, 122 biopsies). The control group encompassed 7 donor heart fragments. Proliferation in biopsies was evaluated with Ki67 (M7240, DAKO), cardiocyte hypertrophy by measuring their diameter, the surface area of the nuclei, nuclear-sarcoplasmic index, and stromal fibrosis evaluated as the surface area fraction. Ultrasound measurements included diastolic thickness of the interventricular septum, posterior wall of the left ventricle, and left ventricular mass. The correlation of measurements with time from transplantation was evaluated using Spearman's test. RESULTS: A positive Ki67 reaction was observed in fibroblasts and endothelial cells. The increased cardiocyte nuclear area correlated with the time elapsed since transplantation (r = 0.2; P < .05) with a simultaneous decrease in cardiocyte thickness (r = -0.3; P < .05), without changes in the nuclear-cytoplasmic index (r = 0.02; P > .05). Stromal fibrosis also increased (r = 0.1; P < .05). Ultrasound measurements of the left ventricle showed a decreased tendency with the passage of time (r = -0.2 to -0.3; P < .05). CONCLUSION: A transplanted heart does not undergo hypertrophy but rather fibrous atrophy with apparent compensatory hypertrophy of the cardiomyocytes.

Cardiocyte nucleus shape as an indicator of heart graft aging.

UNLABELLED: Morphometric publications based on the measurement of cardiocyte nuclei indicated their progressive hypertrophy ignoring, however, their shape, which is a deciding factor for the microscopic-based diagnosis of hypertrophy. We sought was to demonstrate how the shapes of cardiocyte nuclei change over time and correlate them with the thickness of the interventricular septum, (IVS) the biopsy site. MATERIAL: We evaluated myocardial biopsies taken in the first week, first month, and then annually until posttransplant year 10. Only biopsies with no rejection were considered: grade "0" ISHLT (122 biopsies). The control group encompassed fragments from seven donor hearts. METHODS: Cardiomyocyte nuclei were evaluated morphometrically. We calculated the length, breadth, perimeter, roundness, elongation, and fullness factors for correlation with the IVS thickness, and selected indices. The relationships between karyometry and IVS thickness (measured by ultrasound) as well as time were calculated by Spearman's correlation test. RESULTS: Among the examined indices, only nuclear length did not correlate significantly with follow-up time. Among the remaining indices, the strongest correlations with time were observed with regard to breadth (r = 0.214), perimeter (r = 0.150), roundness (r = -0.06) and fullness (r = 0.06), and finally elongation (r = 0.02). The decreasing thickness of the interventricular septum (r = -0.31) showed a weak correlation only with the cardiocyte nuclear length (r = -0.05). CONCLUSION: Graft aging imitates hypertrophy inasmuch as cardiocyte nuclei become wider despite the decreased thickness of the interventricular septum. Therefore, karyometric measurements do not reflect myocardial morphology.

The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise.

Strenuous physical exercise induces muscle fibers damage and non-specific inflammatory response. Activated by inflammatory process cells may serve as the source of wide spectrum of inflammatory mediators and growth factors. Namely Platelet Derived Growth Factor (PDGF), Transforming Growth Factor-beta (TGF-beta) and Vascular Endothelial Growth Factor (VEGF) could be released. The aim of present study was to assess the impact of physical exercise on growth factors generation in healthy young people. 14 young sportsmen were enrolled into the study. They performed strenuous physical exercise. Blood samples were drawn before, immediately after, and 2 hours after the exercise bout. Serum PDGF, TGF-beta and VEGF concentrations were measured using commercially available ELISA kit based on immunoenzimatic method. Serum level of PDGF increased significantly from 1.7 ng/ml before to 4.64 ng/ml (2.73-fold) immediately after, and to 3.3 ng/ml (1.94-fold) 2 hours after exertion. Serum level of TGF-beta increased significantly from 20.58 ng/ml before to 55.37 ng/ml (2.7-fold) immediately after, and to 40.03 ng/ml (1.95-fold) 2 hours after exertion. Serum level of VEGF increased significantly from 91.83 pg/ml before to 165.61 pg/ml (1.8-fold) immediately after the exercise. Two hours after the exertion serum level of VEGF was 137.22 pg/ml, what is 1.49-fold above the basal level; however not being significantly different. In summery, observed increased level of growth factors could be involved in the process of adaptation of human organism to physical training. In addition, in the context of the role of inflammation in the pathogenesis of various diseases, our results point to the potentially deleterious effect of strenuous physical exercise.

Supernormal conduction in the accessory pathway of patients with overt or concealed ventricular pre-excitation.

It was recently shown that supernormal conduction in the diseased His-Purkinje system is more common than previously thought, and is always associated with prolongation of refractoriness. To assess whether supernormal conduction could also occur in the accessory pathway of patients with ventricular pre-excitation, 21 patients with manifestly prolonged refractoriness in the accessory pathway were studied. Under these conditions, programmed atrial stimulation revealed a phase of supernormal conduction in 16 (76%) of the 21. Therefore, what was believed to be a nonexistent or exceptional physiologic event was shown to be a rather common finding, at least under certain circumstances. Supernormal conduction occurred in all 7 patients with an anterograde refractory period of 480 to 980 ms, and in 5 of 10 patients with a refractory period greater than 1.0 second or with no anterograde conduction. Supernormal conduction could not be demonstrated in four patients with a refractory period less than or equal to 440 ms, but appeared in all four patients after the refractory period was prolonged by a rapid rate of stimulation or administration of ajmaline. The electrophysiologic changes underlying the occurrence of supernormal conduction in the accessory pathway are similar to those previously reported for the bundle branch system. The demonstration of supernormal conduction in the accessory pathway may uncover the presence of concealed ventricular pre-excitation. Supernormal conduction over the accessory pathway may facilitate a rapid ventricular response during atrial fibrillation, even if the refractory period is prolonged.

Increased sensitivity of the arterial chemoreceptor drive in young men with mild hypertension.

Ventilatory, airway occlusion pressure, arterial blood pressure and heart rate responses to isocapnic progressive hypoxia and to hypercapnia in high oxygen, both induced by a rebreathing method, were measured in 20 hypertensive male subjects aged 20 to 21 years with a diastolic blood pressure of 13.1 KPa +/- 0.34 SD (98 mmHg +/- 2.6 SD) and in 20 age-matched normotensive male subjects. Ventilatory, airway occlusion pressure and blood pressure response to hypoxia was significantly greater in the hypertensive subjects. Hypoxic ventilatory drive measured as the parameter A denoting the shape of the V1-O2 curve was 28.8 +/- 2.7 SEM (range 7.0 to 44.2) in the normotensive group and 116.1 +/- 10.5 SEM (range: 71.6 to 234.77) in the hypertensive group, the difference being highly significant (P less than 0.001). The magnitude of respiratory sinus arrhythmia (RSA) recorded during progressive hypoxia and plotted against either PA. O2 or VI values was significantly greater in the hypertensive group. The difference in ventilatory and circulatory responses to hyperoxic hypercapnia between the two groups of subjects was not significant. There was a significant correlation between the responses to hypoxia and hypercapnia in the normotensive subjects (r = 0.56, t = 2.861, P less than 0.01) but no correlation in the hypertensive subjects (r = 0.07). It is concluded that dissociation of the responsiveness of the peripheral and central chemosensitivity, the former being significantly increased and predominant, occurs in early, mild hypertension.

Arterial hypertension due to occlusion of the adrenal vein in the rat is strain-dependent.

OBJECTIVE: To determine whether the development of arterial hypertension due to occlusion of the central adrenal vein in the rat is strain-dependent DESIGN AND METHODS: The experiments were performed on male rats weighing 300-400 g each, of the following strains: Wistar outbred, Wistar Glaxo, Lewis, Wistar-Kyoto (WKY) rats bred for high blood pressure (138 +/- 13.2 mmHg), WKY rats bred without the control of blood pressure (118 +/- 12.9 mmHg) and borderline hypertensive rats (BHR). BHR were the F1 spontaneously hypertensive rat and WKY rat crossbred rats. In order to increase blood flow through the adrenal-renal portal circulation, both central adrenal veins of rats in the experimental group were occluded. The systolic blood pressure was measured indirectly by a photoelectric method. RESULTS: By the ninth day after surgery systolic blood pressure had increased significantly only in the WKY rats bred for high blood pressure and BHR, reaching maximal values on 12th day for WKY rats bred for high blood pressure (167 +/- 5 mmHg) and on the 18th day for BHR (170 +/- 14 mmHg). CONCLUSIONS: These data show that the development of arterial hypertension due to augmentation of adrenal blood flow through adrenal-renal portal circulation occurs in rats of strains with a genetic background of hypertension.

Potent V2/V1a vasopressin antagonists with C-terminal ethylenediamine-linked retro-amino acids.

We report the solid-phase synthesis and antagonistic potencies of 25 analogues (1-25) of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-ethyl-D-tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-Tyr(Et)2-VAVP) (A) and of the related Ile4 (D) and [D-Phe2,Ile4] (E) analogues, potent antagonists of the antidiuretic (V2-receptor) and of the vasopressor (V1a-receptor) responses to arginine-vasopressin (AVP). Six of these peptides (1, 13, 17, 19, 21, and 23) have the Pro-Arg-Gly-NH2 tripeptide side chain fully or partially replaced or extended by ethylenediamine (Eda). The remaining 19 peptides have L- or D-amino acids retrolinked to these six C-terminal Eda peptides. Peptides 1, 13, 17, and 19 all have the ring structure of (A). Their side-chain structures are as follows: 1, Eda; 13, Pro-Eda; 17, Pro-Arg-Eda; 19, Arg-Gly-Eda. Peptide 21 is the Pro-Arg-Eda analogue of D; peptide 23 is the Pro-Arg-Gly-Eda analogue of E. Peptide 2 is the retro-Arg analogue of 1. Its side-chain structure is Eda<--Arg. Peptides 3-6 are analogues of 2 which have the D-Tyr-(Et)2 residue replaced by L-Tyr(Et)2 (3), D-Phe2 (4), D-Ile2 (5), or D-Leu2 (6), respectively. Peptides 7-12 are analogues of 2 which have the C-terminal retro-Arg replaced in retrofashion by D-Arg (7), Gly (8), Orn (9), D-Orn (10), D-Lys (11), or Arg-Arg (12). Peptides 14-16 have D-Orn (14), D-Lys (15), and D-Arg (16) retrosubstituted to peptide 13. Peptides 18, 20, and 22 are the retro-Arg-substituted analogues of 17, 19, and 21, respectively. Peptides 24 and 25 have Val and D-Val in retrolinkage with 23, respectively. All 25 peptides were examined for agonistic and antagonistic potencies in AVP V2/V1a assays. With the exception of peptides 5 and 6, all exhibit potent anti-V1a antagonism, with anti-V1a pA2 values in the range 7.64-8.33.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrocardiographic changes evoked by ajmaline in chronic Chagas' disease with manifest myocarditis.

Conversion from Chagas' infection to chagasic myocarditis occurs slowly and the earliest signs of myocardial involvement are hard to define. To obtain new information on this difficult clinical problem, ajmaline was administered (1 mg/kg body weight intravenously) to 101 patients with Chagas' infection and to 46 patients without such infection (control group). In 3 patients in the control group left anterior hemiblock alone occurred whereas in the group with Chagas' infection, ajmaline caused the occurrence of right bundle branch block, left anterior hemiblock, or both, in 32 patients (31.6 percent), ventricular extrasystoles in 8 (7.9 percent) and ischemic ST-T changes in 7 (6.9 percent). Ajmaline may thus evoke the most typical electrocardiographic changes of chronic chagasic myocarditis in patients without signs of myocardial involvement or only minor nonspecific signs. A positive ajmaline test, defined in the present context as the occurrence of a fascicular block, ventricular arrhythmias or ischemic ST-T changes, may indicate the existence of localized areas of injured myocardial tissue, not enough to alter the electrocardiogram by itself, but able to give rise to severe abnormalities after exposure to the drug. The test may therefore be used as a nonspecific detector of myocardial damage, and thus may have a much broader scope of clinical application. In chronic Chagas' infection, the ajmaline test is a relatively simple and apparently safe procedure that may serve to unveil the earliest signs of chagasic myocarditis.

Comparative effects of ajmaline on intermittent bundle branch block and the Wolff-Parkinson-White syndrome.

Phase 4 or phase 3 block or both occurred in the His bundle branch system of 11 patients with intermittent bundle branch block and in the anomalous bundle of 6 of 46 patients with the Wolff-Parkinson-White syndrome (13%). Administration of a single dose of ajmaline (50 mg intravenously) in these patients caused a similar response: expansion of the range of phase 3 and phase 4 block at the expense of the intermediate normal conduction range and total interruption of conduction in the affected fascicle when the effect of the drug was maximal. The great similarity in physiologic behavior and pharmacologic response in these groups of patients suggests that the anomalous bundle was probably diseased or abnormal in the six patients with Wolff-Parkinson-White conduction. In addition, ajmaline caused the first appearance of phase 4 or phase 3 block, or both, but not total interruption of conduction in 26 of the 46 patients with Wolff-Parkinson-White conduction (56.5%). Ajmaline does not cause fascicular block in normal subjects; thus this finding suggests either that the anomalous bundle is diseased or that the safety margin for conduction in the anomalous bundle is much narrower than in the bundle branch system. The conduction-depressing action of ajmaline may be greater at relatively rapid or relatively slow rates of stimulation, and smaller or absent at intermediate rates.

Clinical efficacy of amiodarone as an antiarrhythmic agent.

Amiodarone, administered orally in doses of 200 to 600 mg/day, was remarkably effective in the treatment and prevention of a wide variety of atrial and ventricular arrhythmias. Total suppression and control was provided in 98 (92.4 percent) of 106 patients with supraventricular arrhythmias and in 119 (82 percent) of 145 patients with ventricular arrhythmias. The rates of total control of the arrhythmia were: 96.6 percent in 30 patients with recurrent atrial flutter or fibrillation, 96.6 percent in 59 patients with repetitive supraventricular tachycardia, 100 percent in 27 patients with Wolff-Parkinson-White syndrome and 77.2 percent in 44 patients with recurrent ventricular tachycardia unsuccessfully treated with other drugs. Excellent results were obtained in 6 to 8 patients with repetitive ventricular tachycardia and ventricular fibrillation related to postinfarction ventricular aneurysm and in 12 of 14 patients with ventricular extrasystoles and ventricular tachycardia related to Chagasic myocarditis. Amiodarone proved safe in patients with severe congestive heart failure and severe myocardial damage. Its clinical efficacy was related to its electrophysiologic properties and to two unique properties: its wide safety margin and its cumulative effect. The latter liberates patients from a rigid hourly schedule and provides for continuous antiarrhythmic control, days and even weeks after treatment is discontinued.

Usefulness of the ajmaline test in patients with latent bundle branch block.

Twelve patients were studied with intermittent bundle branch block whose conduction disturbance disappeared completely and could no longer be recorded even after provoked changes in heart rate. Premature atrial stimulation and atrial pacing at rapid rates were performed in nine patients; in none of these nine were these procedures able to evoke the complete bundle branch block pattern that all patients exhibited before the spontaneous normalization of conduction. In marked contrast, the administration of ajmaline (1 mg/kg body weight, intravenously in 90 seconds) caused the bundle branch block pattern to reappear in 10 (83.3 percent) of the 12 patients 30 to 120 seconds after the end of the injection, and in 11 patients (91.6 percent) when additional atrial stimulation was performed in 1 of the 2 "failures." This pharmacologic test was much more rapid and simple than electrophysiologic testing and it was noninvasive. Results of this study suggest that some form of subclinical fascicular injury was present (or had persisted) at a time when intraventricular conduction was persistently normal even though no significant physiologic alteration could be demonstrated by the atrial stimulation techniques. The ajmaline test may become a valuable tool for uncovering cases of latent bundle branch block and furthering our knowledge of the early natural history of intraventricular block.

Potent V2 vasopressin antagonists with structural changes at their C-terminals.

A variety of structural changes were made in the C-terminals of four potent antidiuretic (V2) antagonists. The parent analogs were all derivatives of [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)]arginine-vasopressin, d(CH2)5AVP, namely d(CH2)5[D-Phe2,Ile4]AVP, d(CH2)5[D-Ile2,Ile4]AVP, d(CH2)5[D-Tyr(Et)2, Val4]AVP and d(CH2)5[D-Tyr(Et)2,Ile4]AVP. A number of amino acid amides were substituted for the C-terminal 9-glycinamide without reducing their V2-antagonistic potencies in rats. Many non-amino acid structures were also tolerated at the C-terminals of these antagonists and this end of these peptides can be prolonged without interfering with antagonistic potencies. Such altered V2-antagonists may be useful for the development of radioactive ligands, affinity labels and in affinity columns for studies on antidiuretic receptors. These C-terminal modifications also provide useful information for the further development of potent and specific V2-antagonists which can be valuable pharmacological tools and also promise to become useful clinically for the treatment of excessive water retention.

Effects of new somatostatin analogs on the cell proliferation of colonic crypts and colonic cancers in rats.

The antiproliferative activity of two new somatostatin (SS) analogs: ASS-51 and ASS-52 have been tested in this study. We assessed their ability to inhibit the DNA synthesis in normal colon crypt cells and in the cells of chemically (dimethylhydrazine)-induced colon cancer in the rats. The incorporation of bromodeoxyuridine (BrDU) into appropriate cell nuclei was used as an index of DNA synthesis. It was found that: 1) Only ASS-51 significantly decreases the colon crypt cell proliferation in the rat when compared to controls. Since both analogs were previously shown to inhibit GH release, these data indicate that the antiproliferogenic effect of ASS-51 is independent of the inhibition of GH release. 2) Both examined analogs did not significantly effect the BrDU incorporation into cell nuclei of chemically-induced colon cancer.

Reduced hypotensive effect of clonidine after lesions of the nucleus tractus solitarii in rats.

Bilateral electrolytic lesion of the area of the nucleus tractus solitarii (NTS) in rats produced a sustained increase in blood pressure and reduced the hypotensive response to a single dose of clonidine (30 mug/kg, i.v.). The same dose of clonidine evoked a much larger drop in blood pressure in another group of rats in which an equialent increase in blood pressure was produced by bilateral section of the vagosympathetic trunks and occlusion of both carotid arteries. It is concluded that the dorsal part of the medulla oblongata in the area of NTS is an important link in the hypotensive action of clonidine.

Sexual behavior in male rats after nitric oxide synthesis inhibition.

The influence of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) on the copulatory behavior of sexually experienced male Wistar rats was investigated. L-NAME was injected i.p. 10 min before the onset of a session using a dose of 30 mg/kg (L-NAME 30 group), or 60 mg/kg (L-NAME 60 group). The copulatory sessions were terminated after the third ejaculation in the control group or after 1500 s in the L-NAME 30 and L-NAME 60 groups. L-NAME administration reduced the number of rats that achieved ejaculation by 43% and 86% in the L-NAME 30 and 60 groups, respectively. In both experimental groups only a few intromissions and an increased number of mountings were observed. An increase in the number of ultrasonic vocalizations in the 50 kHz band, a dose-dependent effect, was observed. The level of sexual motivation evaluated by mount latency was not influenced by inhibition of NO synthesis.

The adrenal-renal vascular connection contributes to increase in renal vascular resistance during an experimental hypotension in the rat.

The adrenal vascular connection (ARVC) was described for the first time in the cat by Cow (1914) and by other authors in the dog, rat, rabbit and humans. The aim of the present study is to investigate the role of above connection in regulation of renal vascular resistance (RVR), and renal blood flow (RBF) during decrease in blood pressure in the rat. Animals were divided into three groups. In the first group, mean arterial pressure (MAP) was unchanged. In the second and the third group MAP was maintained at 50 mmHg. In addition in the third group, an alpha adrenergic receptor blockade was produced with intravenous infusion of phentolamine. After stabilisation of RBF, in all groups, the tissue between the adrenal gland and the kidney was cut. RBF and MAP were measured and recorded. In the first and the third group, the elimination of ARVC neither influenced RBF nor RVR. In the second group the elimination of ARVC caused increase in RBF and decrease in RVR (p < 0.01). Results of the present study provide the evidence that catecholamines reaching the kidney, directly from the adrenal gland through ARVC, during the severe hypotension are responsible for reducing of renal blood flow and increase in renal vascular resistance in the rat.

Influence of the stimulation of central chemoreceptors on the gastric mucosal blood flow in artificially ventilated and spontaneously breathing rats.

Respiratory failure coincides frequently with the occurrence of gastric ulceration. In advanced respiratory insufficiency hypoxemia is often accompanied by hypercapnia, which is the stimulus for central chemoreceptors as well as for carotid body chemoreceptors. The purpose of the work was to investigate the reflex effect of stimulation of central chemoreceptors on gastric mucosal blood flow (GMBF) in the rat. Central chemoreceptors were stimulated by a gas mixture composed of 10% carbon dioxide, 50% oxide and 40% nitrogen. In artificially ventilated and spontaneously breathing animals, the stimulation of central chemoreceptors caused a significant increase in gastric mucosal vascular resistance, accompanied by a marked decline in blood flow. We hypothesize that in patients with respiratory insufficiency accompanied by hypercapnia, the reflex impairment of GMBF may contribute to gastric ulceration.

The adrenal renal vascular connection plays an essential role in the pathogenesis of renovascular hypertension in the rat.

The adrenal renal portal circulation (ARPC) contributes to decrease in renal blood flow occurring after renal artery clipping. The aim of present study was to determine the role of the ARPC in the development of the renovascular hypertension in 1-kidney 1-clip model in the rat. Experiments were performed on male Wistar rats. In the control group (A) the right nephrectomy and adrenalectomy were done. In the experimental groups renovascular hypertension was produced by clipping the left renal artery (silver clip ID 0.40 mm). In the first of the experimental groups (B) the right nephrectomy and adrenalectomy were done. In the second experimental group (C), for elimination of the ARPC, the right kidney and the left adrenal gland were removed. In the half number of rats from each group plasma renin activity was measured 48 hours after surgery. An increase in SBP was significantly higher in the group B (ARPC intact) than in the group C (ARPC eliminated) (172 +/- 4 vs 144 +/- 2 mmHg, p.<0.01). PRA was significantly higher in the group C than in the group B (39.0 +/- 1.4 vs 31.2 +/- 2.0 mmol/l/min, p.<0.05). In the control group (A) PRA was significantly lower as compared to the both experimental group (2.0 +/- 1.6 mmol/l/min, p.<0.05).

Influence of the stimulation of carotid body chemoreceptors on the gastric mucosal blood flow in artificially ventilated and spontaneously breathing rats.

The cardiovascular effects of the stimulation of arterial chemoreceptors are different in spontaneously breathing and artificially ventilated animals. Respiratory failure and long term sojourn at high altitude coincide frequently with the occurrence of gastric ulceration. In both these situations a profound stimulation of arterial chemoreceptors is present. The purpose of the paper was to investigate the reflex effect of stimulation carotid chemoreceptors on gastric mucosal blood flow in the rat. Arterial chemoreceptors were stimulated by two methods (I) substitution gas mixture of 10% oxygen in nitrogen for room air and (II) direct injection of acid saline ( 0.05 ml, pH = 6.8) into the distal part of left common carotid artery. In artificially ventilated rats stimulation of arterial chemoreceptors caused significant increase in gastric mucosal vascular resistance, accompanied by marked decline in blood flow. This effect was mediated by adrenergic mechanism. On the contrary to artificially ventilated rats, decline of gastric mucosal vascular resistance with concomitant increase in blood flow was found in spontaneously breathing animals. This effect was not abolished either by phentolamine or atropine. As vasodilatatory effect of arterial chemoreceptors stimulation was abolished by bilateral vagotomy, we postulate that non adrenergic and non cholinergic vagal fibers mediate observed vascular changes in gastric mucosa in spontaneously breathing rats. We hypothesize that in artificially ventilated patients with respiratory failure stimulation of arterial chemoreceptors by hypoxemia and or acidosis may contribute to the development of gastric mucosal lesions.