Effects of Carnosine on the Toxicity of Doxorubicin in Rabbits and Mice

Pteridines ◽  
2003 ◽  
Vol 14 (3) ◽  
pp. 94-101 ◽  
Author(s):  
Remigiusz Zieba ◽  
Elzbieta Czarnecka ◽  
Małgorzata Wągrowska-Danilewicz ◽  
Malgorzata Dzielska-Olczak ◽  
Julita Graczyk

Abstract The aim of this study was to establish the effect of naturally occurring antioxidant - carnosine - on the doxorubicin induced cardiotoxicity in a rabbit model. For this purpose we evaluated the influence of doxorubicin administration alone and in a combined therapy with carnosine on the haemodynamic parameters and on the degree of cardiac muscle cells alterations in rabbits. The rabbits were divided into four groups. One group of rabbits was injccted with doxorubicin in a dose of 2 mg kg-1 weekly for 7 weeks to induce congestive heart failure. Another group of rabbits received the same doses of doxorubicin simultaneously with carnosine in a dose of 100 mg kg1 p.o. daily for 9 weeks. Administration of carnosine was started 1 week prior to the first dose of doxorubicin and was ended one week after the administration of the last dose of doxorubicin. The control groups of animals received 0.9% NaCl and carnosine alone. The following haemodynamic parameters were estimated: heart rate, mean arterial pressure, cardiac index, stroke index and total peripheral resistance. Registration of the haemodynamic parameters in rabbits was performed by Doppler method. Carnosine normalised the values of mean arterial pressure in rabbits receiving doxorubicin, and increased the values of cardiac index and stroke index. The influence of carnosine on total peripheral resistance was not statistically significant, but there was a decreasing tendency. The degree of cardiac muscle cell alterations was examined by light microscopy using Mean Total Score technique. The histopathological studies revealed smaller damage of cardiac muscle in rabbits which received doxorubicin and carnosine, in comparison to animals receiving doxorubicin alone. Carnosine seems to be car dioprotective during doxorubicin administration

1978 ◽  
Vol 55 (s4) ◽  
pp. 69s-71s ◽  
Author(s):  
Y. Miura ◽  
K. Kobayashi ◽  
H. Sakuma ◽  
H. Tomioka ◽  
M. Adachi ◽  
...  

1. Plasma noradrenaline concentrations and haemodynamic status were simultaneously studied in young patients with uncomplicated essential hypertension and in age-matched normal controls. 2. Resting plasma noradrenaline in the controls tended to increase slightly, but progressively, with age. The hypertensive subjects had significantly higher plasma noradrenaline concentrations than those in the controls, but these values did not show any age-related variation. The response of plasma noradrenaline to the standing position tended to increase with age in the controls, whereas plasma noradrenaline in the hypertensive subjects showed a wide range of responses without any fixed relationship with age. 3. The cardiac index was significantly greater in the labile hypertensive subjects than in the controls, whereas total peripheral resistance was significantly greater in the sustained hypertensive subjects than in the labile patients and in the controls. Mean arterial pressure in these patients was closely related with the values of total peripheral resistance rather than with the cardiac index. 4. Of the patients with raised plasma noradrenaline 80% showed significantly increased values of either total peripheral resistance or cardiac index. Plasma noradrenaline was correlated significantly to total peripheral resistance, and marginally to mean arterial pressure. 5. These findings support the view that sympathetic nervous overactivity is an important factor underlying the haemodynamic findings in these patients.


1987 ◽  
Vol 253 (6) ◽  
pp. H1335-H1341 ◽  
Author(s):  
T. L. Smith ◽  
T. G. Coleman ◽  
K. A. Stanek ◽  
W. R. Murphy

A new technique is described that allows minute-to-minute recordings of cardiac output and arterial pressure in unanesthetized rats for periods of 24 h and longer. Rats were instrumented with electromagnetic flow probes and arterial catheters. An electrical and hydraulic swivel was interposed between the rat and recording apparatus to allow free range of movement. Data were collected and analyzed once each minute by computer. Average 24-h values (mean +/- SD) for the following hemodynamic variables were determined in eight rats [expressed where appropriate as a function of body weight (BW)]: cardiac output (98.1 +/- 14.7 ml/min), cardiac index (29.2 +/- 4.4 ml.min-1.100 g BW-1), mean arterial pressure (92.5 +/- 7.8 mmHg), heart rate (347 +/- 45 beats/min), peak aortic flow (403 +/- 32 ml/min), stroke volume (282 +/- 26 microliters), stroke volume index (84.4 +/- 8.1 microliters/100 g BW), and total peripheral resistance index (3.26 +/- 0.46 mmHg.ml-1.min.100 g BW). These results provide a data base of hemodynamic values for unanesthetized adult, Sprague-Dawley male rats, which has not been previously available. In addition, cardiac index, mean arterial pressure, and total peripheral resistance index demonstrated diurnal variation. Diurnal variation contributed substantially to the overall variance observed within these variables. Hourly variance was also substantial and indicates the use of continuous recordings for short-term experiments.


1994 ◽  
Vol 19 (2) ◽  
pp. 215-225 ◽  
Author(s):  
Robert W. Gotshall ◽  
Laurie A. Aten ◽  
Sei Yumikura

Orthostatic stress, sitting, results in adjustments of cardiovascular variables to maintain blood pressure and is prominent in a variety of occupations. Sitting serves as the control position for head-out water immersion studies. This study addressed gender differences in the cardiovascular response to prolonged sitting. Ten men and 10 women had cardiovascular measurements in the supine position compared with measurements during 2 hours in the seated position (Sit). Supine cardiovascular measurements were similar for both sexes. Heart rate changed similarly for both sexes with Sit. With Sit, men had elevated mean arterial pressure (9 ± 3%), total peripheral resistance (54 ± 9%), and decreased cardiac index (−27 ± 5%), while women had no change in mean arterial pressure, lesser elevations in total peripheral resistance (17 ± 7%), and lesser decreases in cardiac index (−12 ± 5%) than men. Thus men, compared to women, had an elevated mean arterial pressure response to prolonged orthostatic stress. Key words: posture, cardiac output, blood pressure, peripheral resistance, sex


1993 ◽  
Vol 265 (5) ◽  
pp. H1727-H1733 ◽  
Author(s):  
D. S. Martin ◽  
J. R. Haywood

The present study was undertaken to determine the hemodynamic responses associated with stimulation of the hypothalamic paraventricular nucleus (PVN). Male Sprague-Dawley rats (n = 21) were instrumented with guide cannulas directed bilaterally at the PVN, with an electromagnetic flow probe placed on the ascending aorta and with femoral venous and arterial catheters. Bicuculline methiodide (BMI, 2 mM) was infused bilaterally (100 nl/20 min) into the PVN region before and after treatment with the beta 1-adrenergic antagonist, metoprolol bitartrate (2 mg/kg iv) or the alpha 1-adrenergic receptor antagonist, prazosin hydrochloride (2 mg/kg iv). Infusion of BMI into the PVN increased mean arterial pressure by 17 +/- 2 mmHg, and heart rate rose by 91 +/- 8 beats/min. Cardiac index increased 17 +/- 3%, whereas total peripheral resistance index was not altered significantly. After metoprolol treatment, the mean arterial pressure response to BMI was similar to control (16 +/- 2 mmHg), but the tachycardia was reduced significantly (10 +/- 4 beats/min). In addition, the blood flow response was changed qualitatively. Total peripheral resistance increased 13 +/- 3%, whereas the cardiac index response was abolished (1 +/- 2%). After prazosin treatment, BMI administration into the PVN failed to increase arterial pressure (-1 +/- 4 mmHg). Nevertheless, the BMI infusion was associated with significant hemodynamic effects. Total peripheral resistance index decreased (-24 +/- 6%), whereas cardiac index and stroke volume index increased 34 +/- 8 and 17 +/- 5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


1999 ◽  
Vol 86 (1) ◽  
pp. 285-293 ◽  
Author(s):  
Stephen S. Blevins ◽  
Martha J. Connolly ◽  
Drew E. Carlson

The roles of the carotid arterial baroreceptor reflex and of vagally mediated mechanisms during positive end-expiratory pressure (PEEP) were determined in pentobarbital-anesthetized dogs with isolated carotid sinuses. Spontaneously breathing dogs were placed on PEEP (5–10 cmH2O) with the carotid sinus pressure set to the systemic arterial pressure (with feedback) or to a constant pressure (no feedback). Right atrial volume was measured with a conductance catheter. With carotid baroreceptor feedback before bilateral cervical vagotomy, total peripheral resistance increased ( P < 0.01) and mean arterial pressure decreased (−9.8 ± 4.3 mmHg) in response to PEEP. With no feedback after vagotomy, mean arterial pressure decreased to a greater extent (−45 ± 6 mmHg, P < 0.01), and total peripheral resistance decreased ( P < 0.05) in response to PEEP. In contrast, cardiac index decreased similarly during PEEP ( P < 0.01) for all baroreceptor and vagal inputs. This response comprised a decrease in the passive phase of right ventricular filling ( P< 0.01) that was not matched by the estimated increase in active right atrial output. Although the carotid baroreceptor reflex and vagally mediated mechanisms elicit vasoconstriction to compensate for the effects of PEEP on the arterial pressure, these processes fail to defend cardiac output because of the profound effect of PEEP on the passive filling of the right ventricle.


1973 ◽  
Vol 45 (s1) ◽  
pp. 155s-157s
Author(s):  
J. Tuckman ◽  
J.-L. Benninger ◽  
F. Reubi

1. Stabilized hypertensive haemodialysis patients, as well as those with normotension, had a greatly elevated cardiac index (CI) that was not due to hypervolemia, but was most likely secondary to their anaemic condition. The hypertension itself was not accompanied by hypervolaemia, but was associated with a relatively very high total peripheral resistance. 2. In eight patients with successfully transplanted kidneys the following results were found. (a) Five were clearly hypertensive and had supine mean arterial pressure between 117 and 143 mmHg. It is noted that they were receiving prednisone at the time of the studies. (b) CI was normal in seven. (c) Total blood volume was normal in all. (d) The presence of wide-open arterio-venous fistulae was not associated with an increase in CI.


Cephalalgia ◽  
2019 ◽  
Vol 40 (3) ◽  
pp. 266-277
Author(s):  
Willebrordus PJ van Oosterhout ◽  
Guus G Schoonman ◽  
Dirk P Saal ◽  
Roland D Thijs ◽  
Michel D Ferrari ◽  
...  

Introduction Migraine and vasovagal syncope are comorbid conditions that may share part of their pathophysiology through autonomic control of the systemic circulation. Nitroglycerin can trigger both syncope and migraine attacks, suggesting enhanced systemic sensitivity in migraine. We aimed to determine the cardiovascular responses to nitroglycerin in migraine. Methods In 16 women with migraine without aura and 10 age- and gender-matched controls without headache, intravenous nitroglycerin (0.5 µg·kg−1·min−1) was administered. Finger photoplethysmography continuously assessed cardiovascular parameters (mean arterial pressure, heart rate, cardiac output, stroke volume and total peripheral resistance) before, during and after nitroglycerin infusion. Results Nitroglycerin provoked a migraine-like attack in 13/16 (81.2%) migraineurs but not in controls ( p = .0001). No syncope was provoked. Migraineurs who later developed a migraine-like attack showed different responses in all parameters vs. controls (all p < .001): The decreases in cardiac output and stroke volume were more rapid and longer lasting, heart rate increased, mean arterial pressure and total peripheral resistance were higher and decreased steeply after an initial increase. Discussion Migraineurs who developed a migraine-like attack in response to nitroglycerin showed stronger systemic cardiovascular responses compared to non-headache controls. The stronger systemic cardiovascular responses in migraine suggest increased systemic sensitivity to vasodilators, possibly due to insufficient autonomic compensatory mechanisms.


1975 ◽  
Vol 03 (03) ◽  
pp. 245-261 ◽  
Author(s):  
Do Chil Lee ◽  
Myung O. Lee ◽  
Donald H. Clifford

The cardiovascular effects of moxibustion at Jen Chung (Go-26) in 10 dogs under halothane anesthesia were compared to 5 dogs under halothane anesthesia without moxibustion and 5 dogs under halothane anesthesia in which moxibustion was effected at a neutral or non-acupuncture site. Cardiac output, stroke volume, heart rate, mean arterial pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2 and base deficit were measured over a two-hour period. A significant increase in cardiac output and stroke volume and a significant decrease in the total peripheral resistance were observed in the group which was stimulated by moxibustion at Jen Chun (Go-26). Heart rate, mean arterial pressure and pulse pressure were significantly increase during the early part of the two-hour period in the same group. The cardiovascular effects of moxibustion at Jen Chung (Go-26) which were observed at the end of the two hours were also present in two dogs in which measurements were continued for two additional hours.


1980 ◽  
Vol 238 (4) ◽  
pp. H539-H544 ◽  
Author(s):  
T. L. Smith ◽  
P. M. Hutchins

We studied the effects of three anesthetic agents on the central hemodynamics of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats instrumented with chronic electromagnetic flow probes and arterial pressure catheters. Cardiovascular alterations due to ether, pentobarbital sodium (PBS; 50 mg/kg), and a 2% chloralose-7.5% urethan mixture (CU; 6 ml/kg) were determined. Ether produced significant elevations in heart rate (HR), cardiac index (CI), stroke volume (SV), and peak aortic flow velocity (PAFV) in SHRs (P less than 0.01) and elevations of HR and CI in WKYs (P less than 0.05). Ether reduced total peripheral resistance (TPR) and mean arterial pressure (MAP) in WKYs and SHRs (P less than 0.01). PBS decreased HR, CI, SV, MAP, PAFV, and minute work (MW) in both WKYs and SHRs (P less than 0.05--P less than 0.001). PBS also lowered TPR in WKYs (P less than 0.05). CU produced effects similar to those of PBS, but did not alter HR or TPR. Central hemodynamics are therefore significantly altered by these anesthetics when compared to those of conscious rats. These agents also have differential effects on the hemodynamics of SHRs and WKYs.


2019 ◽  
Vol 71 (6) ◽  
pp. 1846-1852
Author(s):  
C.K. Ido ◽  
P.E.S. Silva ◽  
H.R.A. Silva ◽  
E.G.F. Biteli ◽  
R.L. Carneiro ◽  
...  

ABSTRACT This study aimed to evaluate comparatively the effects of propofol or isoflurane on hemodynamic variables in piglets that received inspired oxygen fraction (FIO2) of 0.5 under spontaneous ventilation. Therefore, sixteen piglets weighing 16±1.1kg, were randomly divided into two groups: GI (Isoflurane and FIO2 of 0.5) and GP (Propofol and FIO2 of 0.5). Heart rate (HR), systolic, diastolic and mean arterial pressure (SAP, DAP and MAP), central venous pressure (CVP), cardiac output (CO), mean pulmonary arterial pressure (mPAP) and mean capillary pulmonary pressure (mCPP) were assessed 40 minutes after anesthetic induction (T0), followed by 15 minutes intervals (from T15 to T60). The variables cardiac index (CI), stroke volume (SV), stroke index (SI), total peripheral resistance (TPR), total peripheral resistance index (TPRI), pulmonary vascular resistance (PVR), and pulmonary vascular resistance index (PVRI) were calculated. SAP and TPRI were significantly different between groups at T30 and T60 (P< 0.05) with higher GP values being recorded. There were no differences in the other variables, however, GP presented mean closer to normality on most of the analyzed variables. Therefore, we conclude that total intravenous anesthesia with propofol presented greater stability of the hemodynamic variables evaluated.


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