Biomedical subjects

C Ribuot

Publications and source records attributed to C Ribuot.

At least 37 records · Page 2Linked to original sources

PubMed1999

Heat stress fails to protect myocardium of streptozotocin-induced diabetic rats against infarction.

OBJECTIVE: Protection conferred by heat stress (HS) against ischaemia-reperfusion injury, in term of mechanical function and myocardial necrosis, has been extensively studied. In contrast, the effects of disease states on this HS-induced cytoprotective response are less known. Therefore, we investigated the effects of prior heat stress on the infarct size in the isolated heart and on the myocardial heat stress protein (HSP) 72 synthesis, in a model of insulin-dependent diabetic rats. METHODS: Three groups of animals were studied: D rats were rendered diabetic by 55 mg/kg streptozotocin i.v. injection. DI rats received the same treatment plus a daily injection of insulin started 2 weeks after and V rats received the vehicle of streptozotocin plus a daily injection of saline. Eight weeks later, D, DI and V rats were either heat-stressed (42 degrees C for 15 min) or sham-anaesthetised. Twenty-four hours later, their hearts were isolated, perfused using the Langendorff technique, and subjected to a 30 min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial HSP72 content was measured 24 h after HS or sham treatment using an electrophoresis coupled with a Western blot analysis. RESULTS: Infarct-to-risk ratio (I/R) was significantly reduced in hearts from heat-stressed (11.7 +/- 2.0%) compared to sham (30.0 +/- 3.2%) V rats. This cardioprotection was not observed in hearts from D (I/R: 31.4 +/- 3.3 vs. 34.3 +/- 3.5%) and DI (I/R: 28.7 +/- 1.6 vs. 30.3 +/- 1.6%) rats. Risk zones were similar between all experimental groups. The incidence of ventricular arrhythmias during ischaemia and reperfusion periods was not different between the six experimental groups. Western blot analysis of the myocardial HSP72 content showed a comparable heat stress-induced increase of this protein, in V, D and DI animals. CONCLUSION: These results demonstrate that myocardial protective effect induced by heat stress could not extend to a pathological animal model like the diabetic rat and seems to be unrelated to the HSP72 level. Further investigations are required to elucidate the precise role of the heat stress proteins in this adaptive response.

Analysis of Variance↗

PubMed1999

Monophosphoryl lipid A, a derivative of bacterial lipopolysaccharide, fails to induce B1-receptor-dependent responses to (des-Arg9)-bradykinin in the rabbit in vivo.

OBJECTIVE: The aim of this study was to evaluate whether monophosphoryl lipid A (MLA) was able to induce a hypotensive response to (des-Arg9)-bradykinin in the rabbit in vivo, by inducing B1-receptor synthesis. MATERIALS AND METHODS: Arterial pressure was measured after intra-arterial administration of B1- and B2-receptor agonists and antagonists in control rabbits and in rabbits pre-treated 24 h earlier with MLA (100 microg kg(-1) i.v.) or lipopolysaccharide (LPS) (10 microg kg(-1) i.v.). RESULTS: Intra-arterial bradykinin administration induced a similar dose-dependent hypotension in all groups (BK 0.25 microg kg(-1), 36 +/- 3 mm Hg, BK 1 microg kg(-1), -39 +/- 3 mm Hg, p < 0.05 vs. control conditions) that was significantly antagonised by intra-arterial HOE 140 (2 microg kg(-1)) (-5 +/- 2 mm Hg, p < 0.05). Intra-arterial (des-Arg9)-bradykinin induced a hypotensive response in the LPS-pre-treated group (DBK 1 microg kg(-1), -6 +/- 1 mm Hg, DBK 10 microg kg(-1), -10 +/- 1 mm Hg, p < 0.05 vs. control conditions) that was totally abolished by intra-arterial (des-Arg9, Leu8)-bradykinin (10 microg kg(-1) min(-1)) (+1 +/- 2 mm Hg, p < 0.05). In the control and MLA-pre-treated groups, (des-Arg9)-bradykinin had no effect. CONCLUSION: MLA pre-treatment did not induce a hypotensive response to (des-Arg9)-bradykinin. We conclude that, in contrast to LPS, MLA does not induce B1-receptor synthesis, 24 h after its administration in the rabbit. Thus, the cardioprotective effects of MLA do not appear to be related to the kinin pathway.

Adjuvants, Immunologic↗

PubMed1999

In vivo demonstration of H3-histaminergic inhibition of cardiac sympathetic stimulation by R-alpha-methyl-histamine and its prodrug BP 2.94 in the dog.

1. The aim of this study was to investigate whether histamine H3-receptor agonists could inhibit the effects of cardiac sympathetic nerve stimulation in the dog. 2. Catecholamine release by the heart and the associated variation of haemodynamic parameters were measured after electrical stimulation of the right cardiac sympathetic nerves (1-4 Hz, 10 V, 10 ms) in the anaesthetized dog treated with R-alpha-methyl-histamine (R-HA) and its prodrug BP 2.94 (BP). 3. Cardiac sympathetic stimulation induced a noradrenaline release into the coronary sinus along with a tachycardia and an increase in left ventricular pressure and contractility without changes in mean arterial pressure. Intravenous administration of H3-receptor agonists significantly decreased noradrenaline release by the heart (R-HA at 2 micromol kg(-1) h(-1): +77 +/- 25 vs +405 +/- 82; BP 2.94 at 1 mg kg(-1): +12 +/- 11 vs +330 +/- 100 pg ml(-1) in control conditions, P < or = 0.05), and increases in heart rate (R-HA at 2 micromol kg(-1) h(-1): +26 +/- 8 vs +65 +/- 10 and BP 2.94 at 1 mg kg(-1): +30 +/- 8 vs 75 +/- 6 beats min(-1), in control conditions P < or = 0.05), left ventricular pressure, and contractility. Treatment with SC 359 (1 mg kg(-1)) a selective H3-antagonist, reversed the effects of H3-receptor agonists. Treatment with R-HA at 2 micromol kg(-1) h(-1) and BP 2.94 at 1 mg kg(-1) tended to decrease, while that with SC 359 significantly increased basal heart rate (from 111 +/- 3 to 130 +/- 5 beats min(-1), P < or = 0.001). 4. Functional H3-receptors are present on sympathetic nerve endings in the dog heart. Their stimulation by R-alpha-methyl-histamine or BP 2.94 can inhibit noradrenaline release by the heart and its associated haemodynamic effects.

Animals↗

PubMed1999

Accurate guidance for percutaneous access to a specific target in soft tissues: preclinical study of computer-assisted pericardiocentesis.

In the field of percutaneous access to soft tissues, our project was to improve classical pericardiocentesis by performing accurate guidance to a selected target, according to a model of the pericardial effusion acquired through three-dimensional (3D) data recording. Required hardware is an echocardiographic device and a needle, both linked to a 3D localizer, and a computer. After acquiring echographic data, a modeling procedure allows definition of the optimal puncture strategy, taking into consideration the mobility of the heart, by determining a stable region, whatever the period of the cardiac cycle. A passive guidance system is then used to reach the planned target accurately, generally a site in the middle of the stable region. After validation on a dynamic phantom and a feasibility study in dogs, an accuracy and reliability analysis protocol was realized on pigs with experimental pericardial effusion. Ten consecutive successful punctures using various trajectories were performed on eight pigs. Nonbloody liquid was collected from pericardial effusions in the stable region (5 to 9 mm wide) within 10 to 15 minutes from echographic acquisition to drainage. Accuracy of at least 2.5 mm was demonstrated. This study demonstrates the feasibility of computer-assisted pericardiocentesis. Beyond the simple improvement of the current technique, this method could be a new way to reach the heart or a new tool for percutaneous access and image-guided puncture of soft tissues. Further investigation will be necessary before routine human application.

Animals↗

PubMed1999

Histamine H3-receptor stimulation is unable to modulate noradrenaline release by the isolated rat heart during ischaemia-reperfusion.

The aim of this study was to evaluate the ability of H3-histaminergic prejunctional receptors to modulate the noradrenaline release induced by myocardial ischaemia in the rat, and the effects of an eventual modulation on haemodynamic, biochemical and electrophysiological parameters. Isolated rat hearts were perfused according to the Langendorff technique. Control hearts (n = 13) were not treated; two groups were treated with the H3-agonist R-alpha-methyl-histamine at 0.3 microM (n = 14) and 1 microM (n = 11) and one group, used as positive control, was treated with the selective alpha 2-agonist Mivazerol at 0.5 microM (n = 14) added to the perfusion medium. Noradrenaline, lactate and transaminase output in the coronary effluent, as well as various haemodynamic and electrophysiological parameters, were measured during global and total ischaemia (30 min) and reperfusion (30 min). alpha 2-receptor stimulation increased ischaemia-induced noradrenaline release during reperfusion (195 +/- 13 vs. 145 +/- 12 pmol.g-1 in control group, P < 0.05). In contrast, R-alpha-methyl-histamine, at both doses, did not significantly modify these parameters. Both treatments did not affect ischaemia- and reperfusion-induced haemodynamic (decrease in heart rate or in left ventricular developed pressure), biochemical (lactate and GOT release) and electrophysiological (arrhythmias or increase in action potential duration) alterations. Unlike other species, the rat appears to be insensitive to H3-histaminergic receptor modulation of ischaemia-induced noradrenaline release, although a modulation can be seen with other prejunctional receptor agonists.

Action Potentials↗

PubMed1999

Heat stress response and myocardial protection.

Prior whole-body hyperthermia is able to protect the myocardium against ischaemia-reperfusion injury by reducing cellular necrosis, preserving the ventricular function and preventing the occurrence of arrhythmias. These cardioprotective effects are associated with reduction of oxidative stress, preservation of the high-energy phosphate levels and synthesis of heat stress proteins. A better understanding of this powerful protective adaptation of the myocytes would be of interest for potential clinical application, and rational design of specific agents that activate this mechanism will hopefully follow soon.

Animals↗

PubMed1998

Heat stress-induced resistance to myocardial infarction in the isolated heart from transgenic [(mREN-2)27] hypertensive rats.

OBJECTIVE: Heat stress (HS) is known to confer protection against ischaemia-reperfusion injury, including mechanical dysfunction and myocardial necrosis. However, the effects of disease states on this HS-induced cytoprotective response are less known. Therefore, we investigated the effects of prior heat stress on the infarct size in the isolated rat heart and on the myocardial heat stress protein (HSP) 72 synthesis, in transgenic [(mREN-2)27] hypertensive (TGH) rats or normotensive (NT) controls. METHODS: TGH or NT rats were either heat stressed (42 degrees C for 15 min) or sham anaesthetised. After 24 h, their hearts were isolated, perfused using the Langengorff technique, and subjected to a 35-min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial HSP72 content was measured 24 h after HS or sham treatment using electrophoresis coupled with Western blot analysis. RESULTS: Infarct-to-risk (I/R) ratio was significantly reduced in HS (15.5 +/- 1.2%) compared to sham (42.2 +/- 2.1%) hearts of NT rats. This reduction in infarct size was maintained in TGH hearts (I/R: 20.0 +/- 1.0 vs. 48.0 +/- 3.8%). Risk zones were similar between all experimental groups. The incidence of ventricular arrhythmias during ischaemia and reperfusion periods was not different between the four experimental groups. Western blot analysis of the myocardial HSP72 content showed a heat stress-induced increase of this protein, in both TGH and NT animals. CONCLUSION: These results demonstrate that the myocardial protective effect induced by heat stress could extend to a pathological animal model like the transgenic [(mREN-2)27] hypertensive rat and is correlated with a myocardial HSP72 induction.

Analysis of Variance↗

PubMed1998

Resistance to myocardial infarction induced by heat stress and the effect of ATP-sensitive potassium channel blockade in the rat isolated heart.

1. Heat stress (HS) is known to protect against myocardial ischaemia-reperfusion injury by improving mechanical dysfunction and decreasing necrosis. However, the mechanisms responsible for this form of cardioprotection remain to be elucidated. ATP-sensitive potassium (K(ATP)) channels have been shown to be involved in the delayed phase of protection following ischaemic preconditioning, a phenomenon closely resembling the HS-induced cardioprotection. The aim of this study was thus to investigate the role of K(ATP) channels in HS-induced protection of the isolated rat heart. 2. Twenty four hours after whole body heat stress (at 42 degrees C for 15 min) or sham anaesthesia, isolated perfused hearts were subjected to a 15 min stabilization period followed by a 15 min infusion of either 10 microM glibenclamide (Glib), 100 microM sodium 5-hydroxydecanoate (5HD) or vehicle (0.04% DMSO). Regional ischaemia (35 min) and reperfusion (120 min) were then performed. 3. Prior heat stress significantly reduced infarct-to-risk ratio (from 42.4+/-2.4% to 19.4+/-2.9, P<0.001). This resistance to myocardial infarction was abolished in both Glib-treated (40.1+/-1.8% vs 42.3+/-1.8%) and 5HD-treated (41.2+/-1.8% vs 41.8+/-1.2%) groups. 4. The results of this study suggest that K(ATP) channel activation contributes to the cytoprotective response induced by heat stress.

Animals↗

PubMed1998

Early effects of acute gamma-radiation on vascular arterial tone.

1. To determine the acute effects of irradiation on the functionality of vessel, rat aortic rings were mounted in an organ bath for isometric tension measurements and irradiated (60Co, 1 Gy min(-1), 15 min). 2. Irradiation, which is without effect on non-contracted or endothelium-denuded vessels, led to an immediate and reversible increase in vascular tone on (-)-phenylephrine (1 microM)-precontracted aortic rings. The tension reached a plateau about 5 min after the beginning of irradiation. 3. The maximal radiation-induced contraction occurred on aortic rings relaxed by acetylcholine (ACh) (1 microM). In this condition, the addition of catalase (1000 u ml(-1)), which reduces hydrogen peroxide, and DMSO (0.1% v/v), which scavenges hydroxyl radical, had no influence on tension level while superoxide dismutase (SOD) (100 u ml(-1)), a superoxide anion scavenger, reduced the observed contraction. A similar result was obtained in the presence of indomethacin (10 microM), a cyclo-oxygenase blocker. 4. Pretreatment of rings with the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME) (10-100 microM) inhibited the radiation-induced contraction. 5. This effect was dose rate-dependent and even occurred for a very low dose rate (0.06 Gy min(-1)). 6. The present results indicate that gamma-radiation induces an instantaneous vascular tone increase that is endothelium and dose rate-dependent. This effect is (i) maximal when nitric oxide (NO) is produced, (ii) greatly reduced by SOD and (iii) inhibited by L-NAME, suggesting a major involvement of complexes between NO and superoxide anion.

Animals↗

PubMed1998

Infarct size-reducing effect of heat stress and alpha1 adrenoceptors in rats.

1. Noradrenaline (NA), which is abundantly released during heat stress (HS), is known to induce both delayed cardioprotection and heat stress protein (HSP) 72 expression by the mediation of alpha, adrenoceptors. Therefore, we have investigated the implication of alpha1 adrenoceptors in HS-induced resistance to myocardial infarction, in the isolated rat heart model. 2. Rats were pretreated with prazosin (1 mg kg(-1), i.p., Praz) or 5-methylurapidil (3 mg kg(-1), i.v., 5MU) or chloroethylclonidine (3 mg kg(-1), i.v., CEC) or vehicle (V) in order to selectively antagonize alpha1, alpha1A and alpha1B adrenoceptors. They were then either heat stressed (42 degrees C for 15 min) or sham anaesthetized. Twenty-four hours later. their hearts were isolated, retrogradely perfused, and subjected to a 30 min occlusion of the left coronary artery followed by 120 min of reperfusion. 3. Infarct-to-risk ratio was significantly reduced in HS+V (15.4+/-1.8%) compared to Sham+V (35.7+/-1.3%) hearts. This effect was abolished in Praz-treated (29.1+/-1.6% in HS+Praz vs 34.1+/-4.0% in Sham+Praz), 5MU-treated (34.5+/-2.2% in HS+5MU vs 31.2+/-2.0% in Sham+5MU) and CEC-treated (33.4+/-3.0% in HS+CEC vs 32.4+/-1.3% in Sham+CEC) groups. Western blot analysis of myocardial HSP72 showed an HS-induced increase of this protein, which was not modified by Praz, 5MU and CEC pretreatments. 4. We conclude that both alpha1A and alpha1B adrenoceptor subtypes appear to play a role in the heat stress-induced cardioprotection, independently of the HSP72 level. Further investigations are required to elucidate the precise role of HSPs in this adaptative response.

Adrenergic alpha-Antagonists↗

PubMed1998

Heat stress-induced B1 receptor synthesis in the rat: an ex vivo study.

1. This ex vivo study was performed to characterize B1 receptor induction in rats submitted to heat stress. Changes in aortic isometric tension were recorded after a 90 min in vitro incubation with [des-Arg9]-bradykinin. B1 receptor mRNA were detected in aorta and heart using RT-PCR technique. 2. Aortic rings from sham rats did not respond to [des-Arg9]-bradykinin. In contrast, this agonist induced a concentration-dependent relaxation of aortic rings from rats submitted to lipopolysaccharide (LPS) treatment or to heat stress 24 h earlier. 3. The concentration-dependent relaxation induced by [des-Arg9]-bradykinin on aortic rings from heat-stressed rats was abolished by [des-Arg10]-HOE 140, a selective B1 receptor antagonist. 4. In endothelium denuded aortic rings from heat-stress rats, [des-Arg9]-bradykinin induced a concentration-dependent constriction. 5. Pretreatment of intact aortic rings from heat-stress rats with the cyclo-oxygenase inhibitor, diclofenac (1 microM) did not prevent the concentration-dependent relaxation in response to [des-Arg9]-bradykinin. In contrast. NO synthase inhibition with N(omega)-nitro-L-arginine methyl ester (30 microM) totally prevented the vasorelaxant response. 6. B1 receptor mRNA were not detected in aorta and heart from sham animals but were present in tissue from heat-stressed and LPS-treated rats. 7. In conclusion, our results suggest that heat stress induces a transcriptional activation of the B1 receptor gene. The induction of B1 receptors leads to an endothelium- and NO-dependent vasorelaxant response to [des-Arg9]-bradykinin.

Animals↗

PubMed1998

Myocardial beta-adrenergic reactivity in volume overload-induced cardiac hypertrophy in the rat.

The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac volume overload. Aortocaval shunt (ACS) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoproterenol dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index were evaluated in plasma and heart ventricles, while beta-adrenoceptor characteristics in ventricle homogenates and slices with [125I]iodocyanopindolol, and the beta(1)/beta(2)-adrenoceptor ratio were estimated. Four weeks of cardiac volume overload resulted in a 55% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 3.9 +/- 0.1 mg/g in sham and ACS rats, respectively) and a 20% increase in protein contents (from 11.3 +/- 0.7 to 13.8 +/- 1.1 mg/100 mg ventricles in sham and ACS rats, respectively). Furthermore, NA and A concentrations and NA turn-over index were increased in ACS rats (14, 40 and 80% versus sham, respectively). A shift to the right of the responses in heart rate, left ventricular systolic pressure, +dP/dtmax and -dP/dtmax responses following increasing doses of isoproterenol was observed, without change in the dose inducing maximum effect. Total beta-adrenoceptor characteristics and beta(1)/beta(2) ratio were unchanged. However, beta(1)-adrenoceptor density increased in epicardium while decreasing in endocardium of left ventricle from ACS rats. Rightward shift at lower doses of isoproterenol-induced cardiac responses in volume-overloaded rats are not likely due to overall beta-adrenoceptor density changes.

Adrenergic beta-Agonists↗

PubMed1998

Myocardial beta-adrenergic reactivity in pressure overload-induced cardiac hypertrophy in the rat.

The purpose of this study was to evaluate the changes in myocardial beta-adrenergic reactivity in animals undergoing a 4 week cardiac pressure-overload. Abdominal aortic constriction (AAC) or sham operation (sham) were performed in male Wistar rats, and 4 weeks later, isoprenaline dose-effects (chronotropic, inotropic and lusitropic properties) were studied after pithing. Noradrenaline (NA) and adrenaline (A) concentrations and NA turn-over index (DHPG /NE ratio) were evaluated in heart ventricles, while beta-adrenoceptor characteristics in ventricle homogenates and slices with [125I]iodocyanopindolol and the beta (1)/beta (2)-adrenoceptor ratio were estimated. Four weeks of cardiac pressure overload resulted in a 70% increase in ventricle weight/body weight ratio (from 2.5 +/- 0.1 to 4.2 +/- 0.3 mg/g in sham and AAC rats, respectively) and a 24% increase in protein contents (from 11.3 +/- 0.7 to 14.0 +/- 1.1 mg/100 mg ventricle in sham and AAC rats respectively). The ventricle NA content was similar in AAC and sham, while the ventricle A content and NA turn-over index were significantly increased in AAC rats (35 and 80% vs sham, respectively). Dose response of isoprenaline was significantly shifted to the right for all studied effects in AAC rats. However, maximal response (in relative values) was similar in AAC and sham rats only for heart rate but not for parameters depending on left ventricle contractile response. The beta-adrenoceptor density was significantly decreased in AAC by 30% without apparent affinity change and due to decreases in beta (1)-sites in septum and to beta (1)- and beta (2)-adrenoceptors in left ventricle endocardium. Decreases in isoprenaline-induced cardiac responses in AAC rats are associated with beta (1)-adrenoceptor density reduction and modification of beta (1)- and beta (2)-adrenoceptor ratio. These modifications are not the only reason for such dose response changes, at least for contractile response.

Adrenergic beta-Agonists↗

PubMed1997

Computer assisted pericardial puncture: work in progress.

Until now, computer assisted surgery has focused primarily on surgical procedures involving rigid anatomical structures. Because soft tissues can be highly mobile and deformable, they may require specific imaging devices, suitable modeling tools, and guiding systems. Percutaneous pericardial puncture is a good clinical target for computer assisted surgery; this procedure is often performed without direct visualization and is dangerous even though echographic control is used. Computer assistance can greatly improve this technique and will allow accurate puncture of preplanned targets. This paper describes a new approach for computer assisted pericardial punctures (CASPER) and describes a first feasibility analysis of CASPER demonstrated with anesthetized animals. The approach is based on the use of echographic data localized in space, from which an optimal strategy is defined. Because of the specificity of the pericardial effusion, a stable target can be selected despite the heart motions. A passive guiding system is used. We have demonstrated the feasibility of the approach.

Animals↗

PubMed1997

In vitro antiarrhythmic effect of prior whole body hyperthermia: implication of catalase.

The protective effect of heat stress against mechanical dysfunction and myocardial necrosis after prolonged ischemia is well known. We have investigated whether the protective effect of heat stress extends to reperfusion arrhythmias in the isolated perfused rat heart. Rats were exposed to 20 min of 42 degrees C hyperthermia. Twenty-four h later their hearts were isolated, perfused and subjected to a 5-min period of occlusion of the left coronary artery. The incidence and duration of reperfusion arrhythmias were assessed in the 30-min reperfusion period. Prior heat stress led to a reduction in the incidence (from 100 to 60%, P</=0.05) and duration (from 611+/-251 to 62+/-51 s, P</=0.05) of ventricular tachycardia and/or fibrillation, upon reperfusion following a 5-min ischemic period. This prevention of reperfusion arrhythmias was associated with a two-fold increase in endogenous catalase activity and an enhanced heat stress protein hsp 72 and 27 expression. Catalase inhibition by 3-amino triazole (AT) abolished the antiarrhythmic effect of heat stress. The incidence (80 v 100%) and duration (691+/-238 v 989+/-242 s) of reperfusion arrhythmias were not different between the group heat shocked + AT and the group treated only with AT. On the other hand, in the presence of AT, myocardial noradrenaline release was attenuated by prior heat stress (upon stabilization: 3.9+/-0.8 compared to 9.4+/-2.1 pg/ml/g tissue, P</=0.05; upon reperfusion: 42.7+/-7.3 compared to 69.8+/-9.5 pg/ml/g tissue, P</=0.05). In conclusion, heat stress leads to protection against reperfusion arrhythmias occurring after a short ischemic insult, in the isolated rat heart. Heat stress proteins and catalase seem to be implicated in this protective effect. Finally, we have shown that in presence of AT, heat stress decreases myocardial noradrenaline release.

Animals↗

PubMed1997

Protein kinase C is involved in resistance to myocardial infarction induced by heat stress.

Heat stress (HS) is known to protect against mechanical dysfunction and myocardial necrosis in myocardial ischemia-reperfusion models both in vivo and in vitro. However, the mechanisms involved in this form of cardioprotection remain unclear. Protein kinase C (PKC) and tyrosine kinase activation have both been shown to be involved in the delayed phase of protection following ischemic preconditioning, a phenomenon which appears to be analogous to HS-induced protection. Therefore, we investigated the role of PKC and tyrosine kinase in HS-induced resistance to myocardial infarction, in the isolated rat heart. The selective inhibitors chelerythrine (Che) and genistein (Gen) were used to inhibit PKC and tyrosine kinase, respectively. Rats were treated with Che (5 mg/kg, i.p.) or Gen (5 mg/kg, i.p.) or vehicle before they were either heat stressed (42 degrees C for 15 min) or sham anesthetized. Twenty-four h later their hearts were isolated, retrogradely perfused, and subjected to 35-min occlusion of the left coronary artery followed by 120-min of reperfusion. Infarct-to-risk ratio was significantly reduced in HS (19.9+/-1.1%) compared to sham (43.1+/-1.1%) hearts. This reduction in infarct size was abolished in chelerythrine-treated groups (43.8+/-1.9% in HS+Che v 44.9+/-2.0% in sham+Che), but was conserved in genistein-treated groups (17.7+/-0.9% in HS+Gen v 36.4+/-2.8% in sham+Gen). In order to confirm that genistein at this dose was effectively inhibiting tyrosine kinase activity, we observed the ability of the agent to prevent the hypoglycemic responses to insulin in a separate group of anesthetised rats receiving an i.v. insulin infusion. Western blot analysis of the myocardial hsp72 showed a HS-induced increase of this protein, which was modified by neither the PKC inhibitor, chelerythrine, nor the tyrosine kinase inhibitor, genistein. We conclude that the activation of PKC, but not of tyrosine kinase, appears to play a role in the functional cardioprotection associated with the heat stress response. Although protection appears to be dissociated from induction of hsp72, further work is required to explore the importance of hsp72 phosphorylation to cytoprotective activity of the protein.

Alkaloids↗

PubMed1997

Reflex adrenal medullary secretion during coronary occlusion mediated by cardiac receptors with afferent vagal fibres in the rat.

The relative contribution of ventricular receptors and sinoaortic baroreceptors to the reflex release of adrenaline upon coronary occlusion was studied in anaesthetised rats submitted to a 30-min occlusion of the left coronary artery. Arterial adrenaline concentrations, heart rate and blood pressure were evaluated in control and sham-operated rats, and following sinoaortic denervation (SAD), bilateral vagotomy with and without SAD, ventricular application of lidocaine, neonatal treatment with capsaicin and cervical section of teh spinal cord. In all groups submitted to coronary ligation, blood pressure decreased sharply upon ligation and remained significantly reduced throughout occlusion while heart rate changes were not significant. In control rats, arterial adrenaline concentrations were significantly increased 15 and 30 minutes following coronary occlusion. The increase in adrenaline concentrations observed upon coronary ligation following SAD was not different from that of the control group. On the other hand, vagotomy with or without SAD, ventricular application of lidocaine, neonatal capsaicin treatment and spinal section all greatly reduced the increase in plasma adrenaline values. These results suggest that a large part of the reflex release of adrenaline upon coronary occlusion is mediated by ventricular receptors with unmyelinated vagal afferent fibres.

Adrenal Medulla↗

PubMed1997

In vivo evidence for B1-receptor synthesis induction by heat stress in the rat.

A hypotensive effect of intravenously injected [des-Arg9]-bradykinin was found in Wistar rats following acute heat stress. This effect was similar to that of intravenously injected bradykinin and was observed 6, 18 and 24 h following an increase in rectal temperature at 42 degrees C for 20 min (H6, H18 and H24 groups, respectively). In contrast, [des-Arg9-bradykinin had no effect on blood pressure in control or sham conditions, early on (3 h) or later on (72 h) after heat stress (Ctl, H3 and H72 groups, respectively), while the response to bradykinin was maintained. The hypotension induced by [des-Arg9]-bradykinin in groups H6, H18 and H24 was comparable to that induced in rats pretreated with a small amount of endotoxin 24 h earlier (LPS group). The hypotensive response in group H24 was totally blunted by [des-Arg10]-Hoe 140 (a potent B1 receptor antagonist) infused at a rate of 10 microg min(-1). These results suggest that heat stress induces the synthesis of vascular B1 receptors in the rat.

Animals↗