A Brief Regional Ischemic-reperfusion Enhances Propofol-induced Depression in Left Ventricular Function of in situ  Rat Hearts

2004 ◽  
Vol 101 (4) ◽  
pp. 879-887 ◽  
Author(s):  
Naoya Kuzumoto ◽  
Yutaka Kitagawa ◽  
Koichi Uemura ◽  
Takashi Ueyama ◽  
Ken-ichi Yoshida ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Inhibitory Effects ◽  
Ischemic Reperfusion ◽  
Kinase C ◽  
Rat Hearts

Background Propofol is short-acting intravenous general anesthetics that reduces cardiovascular hemodynamics. The effects of propofol on intrinsic myocardial contractility, however, remain debatable. The aim of the current study was to test the hypothesis that inhibitory effects of propofol on left ventricular (LV) contractility and mechanical work capability of in situ ejecting rat hearts are attenuated after a brief regional ischemia and reperfusion. Methods The authors obtained steady-state LV pressure-volume loops and intermittently obtained LV end-systolic pressure-volume relation and evaluated effects of propofol on LV function by end-systolic pressure (ESPmLVV), systolic pressure-volume area (PVAmLVV) at midrange LV volume (mLVV). Results Propofol (5.2 +/- 0.3 approximately 11.1 +/- 3.7 microg.ml) significantly decreased ESP0.08 to 78 +/- 12% approximately 64 +/- 13% of prepropofol and PVA0.08 to 76 +/- 13%approximately 63 +/- 16% of prepropofol in normal hearts, whereas propofol at a lower concentration (4.1 +/- 1.0 microg/ml) did not. Although brief ischemic-reperfusion per se did not affect LV function, propofol after that, even at a lower concentration (4.1 +/- 1.0 microg/ml), significantly decreased ESP0.08 to 70 +/- 27% of prepropofol and PVA0.08 to 68 +/- 33% of prepropofol. Pretreatment with a protein kinase C (PKC) inhibitor, bisindolylmaleimide reduced the propofol (4.1 +/- 1.0 microg/ml)-induced greater decreases in ESP0.08 and PVA0.08 after brief ischemic-reperfusion to 94 +/- 33% and 92 +/- 39% of prepropofol. In the propofol-infused hearts after brief ischemic-reperfusion, protein kinase C-epsilon translocation to the nucleus-myofibril fraction was found. Conclusion In contrast to the study hypothesis, brief ischemic-reperfusion enhanced the inhibitory effects of propofol on LV systolic function; this enhancement is attributable to activation of protein kinase C.

Experimental Conditions Are Important Determinants of Cardiac Inotropic Effects of Propofol

2005 ◽  
Vol 103 (5) ◽  
pp. 1026-1034 ◽  
Author(s):  
Noriaki Kanaya ◽  
Brad Gable ◽  
Peter J. Wickley ◽  
Paul A. Murray ◽  
Derek S. Damron
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Stimulation Frequency ◽  
Inhibitory Effects ◽  
Inotropic Effects ◽  
Kinase C ◽  
Developed Pressure ◽  
Perfused Hearts

Background The rationale for this study is that the depressant effect of propofol on cardiac function in vitro is highly variable but may be explained by differences in the temperature and stimulation frequency used for the study. Both temperature and stimulation frequency are known to modulate cellular mechanisms that regulate intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity in cardiac muscle. The authors hypothesized that temperature and stimulation frequency play a major role in determining propofol-induced alterations in [Ca2+]i and contraction in individual, electrically stimulated cardiomyocytes and the function of isolated perfused hearts. Methods Freshly isolated myocytes were obtained from adult rat hearts, loaded with fura-2, and placed on the stage of an inverted fluorescence microscope in a temperature-regulated bath. [Ca2+]i and myocyte shortening were simultaneously measured in individual cells at 28 degrees or 37 degrees C at various stimulation frequencies (0.3, 0.5, 1, 2, and 3 Hz) with and without propofol. Langendorff perfused hearts paced at 180 or 330 beats/min were used to assess the effects of propofol on overall cardiac function. Results At 28 degrees C (hypothermic) and, to a lesser extent, at 37 degrees C (normothermic), increasing stimulation frequency increased peak shortening and [Ca2+]i. Times to peak shortening and rate of relengthening were more prolonged at 28 degrees C compared with 37 degrees C at low stimulation frequencies (0.3 Hz), whereas the same conditions for [Ca2+]i were not altered by temperature. At 0.3 Hz and 28 degrees C, propofol caused a dose-dependent decrease in peak shortening and peak [Ca2+]i. These changes were greater at 28 degrees C compared with 37 degrees C and involved activation of protein kinase C. At a frequency of 2 Hz, there was a rightward shift in the dose-response relation for propofol on [Ca2+]i and shortening at both 37 degrees and 28 degrees C compared with that observed at 0.3 Hz. In Langendorff perfused hearts paced at 330 beats/min, clinically relevant concentrations of propofol decreased left ventricular developed pressure, with the effect being less at 28 degrees C compared with 37 degrees C. In contrast, only a supraclinical concentration of propofol decreased left ventricular developed pressure at 28 degrees C at either stimulation frequency. Conclusion These results demonstrate that temperature and stimulation frequency alter the inhibitory effect of propofol on cardiomyocyte [Ca2+]i and contraction. In isolated cardiomyocytes, the inhibitory effects of propofol are more pronounced during hypothermia and at higher stimulation frequencies and involve activation of protein kinase C. In Langendorff perfused hearts at constant heart rate, the inhibitory effects of propofol at clinically relevant concentrations are more pronounced during normothermic conditions.

Reversible effects of isoproterenol-induced hypertrophy on in situ left ventricular function in rat hearts

2004 ◽  
Vol 287 (1) ◽  
pp. H277-H285 ◽  
Author(s):  
Yutaka Kitagawa ◽  
Daisuke Yamashita ◽  
Haruo Ito ◽  
Miyako Takaki
Keyword(s):  
Cardiac Hypertrophy ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Osmotic Minipump ◽  
Good Index ◽  
Rat Hearts ◽  
Lv Volume ◽  
Work Capability

The aim of the present study was to evaluate specifically left ventricular (LV) function in rat hearts as they transition from the normal to hypertrophic state and back to normal. Either isoproterenol (1.2 and 2.4 mg·kg−1·day−1 for 3 days; Iso group) or vehicle (saline 24 μl·day−1 for 3 days; Sa group) was infused by subcutaneous implantation of an osmotic minipump. After verifying the development of cardiac hypertrophy, we recorded continuous LV pressure-volume (P-V) loops of in situ ejecting hypertrophied rat hearts. The curved LV end-systolic P-V relation (ESPVR) and systolic P-V area (PVA) were obtained from a series of LV P-V loops in the Sa and Iso groups 1 h or 2 days after the removal of the osmotic minipump. PVA at midrange LV volume (PVAmLVV) was taken as a good index for LV work capability ( 13 , 15 , 20 , 21 ). However, in rat hearts during remodeling, whether PVAmLVV is a good index for LV work capability has not been determined yet. In the present study, in contrast to unchanged end-systolic pressure at midrange LV volume, PVAmLVV was significantly decreased by isoproterenol treatment relative to saline; however, these measurements were the same 2 days after pump removal. Simultaneous treatment with a β1-blocker, metoprolol (24 mg·kg−1·day−1), blocked the formation of cardiac hypertrophy and thus PVAmLVV did not decrease. The reversible changes in PVAmLVV reflect precisely the changes in LV work capability in isoproterenol-induced hypertrophied rat hearts mediated by β1-receptors. These results indicate that the present approach may be an appropriate strategy for evaluating the effects of antihypertrophic and antifibrotic modalities.

Regulation of arginine vasopressin mRNA in rat fetal hypothalamic cell culture. Role of protein kinases and glucocorticoids

1993 ◽  
Vol 10 (1) ◽  
pp. 51-57 ◽  
Author(s):  
S-B Hu ◽  
L A Tannahill ◽  
S L Lightman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Protein Kinase A ◽  
Arginine Vasopressin ◽  
In Situ Hybridization Histochemistry ◽  
Kinase C ◽  
Kinase A

ABSTRACT Studies have been performed to investigate the regulation of arginine vasopressin (AVP) mRNA expression in fetal hypothalamic cultures. AVP mRNA-positive neurones were identified by in-situ hybridization histochemistry, and changes in mRNA expression were quantitated by nuclease protection assay. Both protein kinase C and protein kinase A activators increased the expression of AVP mRNA, in contrast to dexamethasone, which inhibited the responses to both protein kinase C and protein kinase A activation.

Volatile Anesthetics Protect the Ischemic Rabbit Myocardium from Infarction

1997 ◽  
Vol 86 (3) ◽  
pp. 699-709 ◽  
Author(s):  
Doris K. Cope ◽  
Keyser W. Impastato ◽  
Michael V. Cohen ◽  
James M. Downey
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Infarct Size ◽  
Adenosine Receptor ◽  
Volatile Anesthetics ◽  
Isolated Hearts ◽  
Anesthetic Agents ◽  
Kinase C ◽  
Adenosine Concentration

Background The influence of anesthetic agents on the infarction process in the ischemic myocardium is unclear. This study evaluated the effects of three intravenous and three inhalational anesthetic agents on myocardial infarction within a quantified ischemic risk zone in rabbit hearts subjected to a standardized regional ischemia-reperfusion insult. Methods Both in vitro and in situ rabbit models were used to investigate the effects of anesthetic agents on infarct size. In all rabbits the heart was exposed and a coronary artery surrounded with a suture to form a snare for subsequent occlusion. In in situ preparations, both intravenous and inhalational agents were tested, whereas only the latter were used in isolated hearts. Infarct size was determined by triphenyltetrazolium chloride staining. To determine whether an adenosine-mediated protective mechanism was involved, 8-(p-sulfophenyl)theophylline, an adenosine receptor blocker, was added to halothane-treated isolated hearts. Adenosine concentration in the coronary effluent was also measured in isolated hearts exposed to halothane. In other protocols, chelerythrine, a highly selective protein kinase C inhibitor, was administered to both halothane-treated and untreated isolated hearts. Results Infarcts in the three in situ groups anesthetized with halothane, enflurane, and isoflurane were about one half as large as infarcts in rabbits that underwent anesthesia with pentobarbital, ketamine-xylazine, or propofol. Volatile anesthetics also protected isolated hearts by a similar amount. Both adenosine receptor blockade and chelerythrine abolished cardioprotection from halothane in isolated hearts. Halothane treatment did not increase adenosine release. Conclusions The volatile anesthetics tested protected the ischemic rabbit heart from infarction, in contrast to the three intravenous agents tested. Protection was independent of the hypotensive effect of the inhalational agents because halothane also protected isolated hearts, in which changing vascular tone is not an issue and coronary perfusion pressure is constant. Cardioprotection by volatile anesthetics depended on both adenosine receptors and protein kinase C, and thus is similar to the mechanism of protection seen with ischemic preconditioning.

Investigation of the inhibitory effects of chelerythrine chloride on the translocation of the protein kinase C βI, βII, ζ in human neutrophils

Il Farmaco ◽  
2001 ◽  
Vol 56 (11) ◽  
pp. 859-865 ◽  
Author(s):  
Xavier Siomboing ◽  
Bernard Gressier ◽  
Thierry Dine ◽  
Claude Brunet ◽  
Michel Luyckx ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Human Neutrophils ◽  
Inhibitory Effects ◽  
Kinase C ◽  
Chelerythrine Chloride

Activation of TxA2/PGH2Receptors and Protein Kinase C Contribute to Coronary Dysfunction in Superoxide Treated Rat Hearts

2000 ◽  
Vol 32 (6) ◽  
pp. 937-946 ◽  
Author(s):  
Sachin A Gupte ◽  
Takao Okada ◽  
Michihiro Tateyama ◽  
Rikuo Ochi
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase C ◽  
Rat Hearts
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