A simple experimental index for the evaluation of inotropic responses

Chan, Samuel H.H.; Ong, B.T.

doi:10.1016/0160-5402(87)90014-3

Cited by 17 publications

(4 citation statements)

References 18 publications

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“…Briefly, a polyethylene catheter filled with heparinized saline (0.9% NaC1) was placed in the common carotid artery of rats in which anesthesia had been induced using 1 glkg i. p. urethane, a dose that is suitable for cardiovascular studies [18]. The heart rate (beats/rain), mean arterial blood pressure (MABP, mmHg), and systemic arterial (SA) dP/dtm~x value (mmHg/s), which is an indirect index of left ventricular contractility [4], were measured. Needle electrodes were inserted under the skin of the animals' legs to record lead-II ECG, and SaT segments (ms) and T waves (gV) were measured and taken as cardiotoxicity end points [7].…”

Section: Methodsmentioning

confidence: 99%

Reduced cardiotoxicity and increased cytotoxicity in a novel anthracycline analogue, 4′-amino-3′-hydroxy-doxorubicin

Danesi

Bernardini

Agen

et al. 1992

Cancer Chemother. Pharmacol.

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The acute and chronic cardiotoxicity and cytotoxicity of the novel doxorubicin (DXR) derivative 4'-amino-3'-hydroxy-DXR were compared with those of 4'-deoxy-DXR and DXR. In the acute cardiotoxicity study, the ECG and hemodynamic changes recorded in anesthetized rats that had been treated i.v. with 10 mg/kg 4'-amino-3'-hydroxy-DXR or 8.6 mg/kg 4'-deoxy-DXR were significantly less severe than those caused by 13 mg/kg DXR. In the chronic cardiotoxicity study, rats received 3 weekly i.v. injections of 3 mg/kg DXR, 3 mg/kg 4'-amino-3'-hydroxy-DXR, or 2 mg/kg 4'-deoxy-DXR during the first 14 days of the study and were observed for an additional 35-day period. DXR induced severe cardiomyopathy that was characterized by ECG changes in vivo (S alpha T-segment widening and T-wave flattening) and by impairment of the contractile responses (Fmax, +/- dF/dtmax) to adrenaline of hearts isolated from treated animals. 4'-Deoxy-DXR caused a progressive enlargement of the S alpha T segment in vivo and a significant impairment of the -dF/dtmax value in vitro, which were less severe than those produced by DXR. The least cardiotoxic drug was 4'-amino-3'-hydroxy-DXR, which induced minor ECG changes without causing significant alterations in the contractile responses of isolated hearts to adrenaline. On the basis of the drug concentration required to inhibit 50% of the colony formation (IC50) of cell lines in vitro, 4'-amino-3'-hydroxy-DXR was less active than 4'-deoxy-DXR but at least twice as active as DXR against human cancer and murine transformed cell lines. These data indicate that 4'-amino-3'-hydroxy-DXR is significantly less cardiotoxic and more cytotoxic than DXR.

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Section: Methodsmentioning

confidence: 99%

Reduced cardiotoxicity and increased cytotoxicity in a novel anthracycline analogue, 4′-amino-3′-hydroxy-doxorubicin

Danesi

Bernardini

Agen

et al. 1992

Cancer Chemother. Pharmacol.

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“…Heart rate was determined by a bio tachometer (Gould G-20-4615-66) triggered by the arterial pulses, and an indirect index for cardiac contractility [14] …”

Section: General Preparationsmentioning

confidence: 99%

Further Characterization of Nociception-Related and Arterial Pressure-Related Neuronal Responses in the Nucleus Reticularis Gigantocellularis of the Rat

Kuo¹,

Yang²,

Chan³

et al. 1996

J Biomed Sci

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The present study was undertaken to further characterize the nucleus reticularis gigantocellularis (NRGC) of the medulla oblongata in the central processing of nociceptive and cardiovascular signals, and its modulation by metenkephalin. In Sprague-Dawley rats anesthetized with pentobarbital sodium, we found that all 125 spontaneously active NRGC neurons that responded to noxious stimuli (tail clamp) also exhibited arterial pressure-relatedness. Forty neurons additionally manifested cardiac periodicity that persisted even during nociceptive responses. While maintaining their cardiovascular responsive characteristics, the nociception-related NRGC neuronal activity was blocked, naloxone-reversibly (0.5 mg/kg, i.v.), by morphine (5 mg/kg, i.v.). Microiontophoretically applied met-enkephalin suppressed the responsiveness of NRGC neurons to individually delivered tail clamp or transient hypertension induced by phenylephrine (5 μg/kg. i.v.). Interestingly, in NRGC neurons that manifested both nociception and arterial pressure relatedness, the preferential reduction in the response to noxious stimuli upon simultaneous elevation in systemic arterial pressure was reversed to one that favored nociception in the presence of met-enkephalin. All actions of met-enkephalin were discemibly blocked by the opioid receptor antagonist, naloxone. Our results suggest that individual NRGC neurons may participate in the processing of both nociceptive and cardiovascular information, or in the coordination of the necessary circulatory supports during nociception. In addition, neuropeptides such as met-enkephalin may exert differential modulation on neuronal responsiveness according to the prevailing physiologic status of the animal. They also showed that NRGC may be a central integrator for pain and cardiovascularrelated functions.

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“…An indirect index for cardiac contractility was pro vided by the first derivative of the arterial pressure signals over time [7], using a differentiator (Grass 7P20). Heart rate was determined by a biotachometer (Grass 7P4) triggered by the arterial pulses.…”

Section: Animal Preparationmentioning

confidence: 99%

Further Elucidation of a Pertussis Toxin-Sensitive Transmembrane Signaling Mechanism Involved in Central α(2)-Adrenoceptor Activation in the Rat

Chen¹,

Lin²,

Chan³

1994

J Biomed Sci

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In adult male Sprague-Dawley rats anesthetized with pentobarbital sodium, we elucidated the molecular consequence of central α(2)-adrenoceptor activation. The hypotensive and negative chronotropic and inotropic actions of the α(2)-adrenoceptor agonist guanabenz were used as our experimental index. Intracerebroventricular administration of pertussis toxin (2.5 µg) significantly attenuated the cardiovascular suppressant effects of the aminoguanidine compound (100 µg/kg i.v.). However, application of N-ethylmaleimide (0.125 or 0.250 µg), phorbol 12- myristate 13-acetate ( 1.25 or 2.50 µg). cholera toxin ( 1.25 or 2.50 µg) or forskolin (12.5 or 25.0 µg) into the lateral cerebral ventricle elicited no appreciable blunting effect on the circulatory depression produced by guanabenz. These results were essentially duplicated when pertussis toxin (0.125 or 0.250 µg), Nethylmaleimide (0.0125 or 0.05 µg), phorbol 12-myristate 13-acetate (0.125 or 0.25 µg). cholera toxin (0.125 or 0.25 µg) or forskolin (1.25 or 2.50 µg) was microinjected bilaterally to the nucleus reticularis gigantocellularis, a medullary site believed to be intimately related to the antihypertensive action of guanabenz. These findings suggest that stimulation of the α(2)-adrenoceptors in the medulla oblongata may result in the activation of a pertussis toxin-sensitive GTP-binding regulatory protein. They further suggest that the biologic signals subsequent to this action may not be linked to Gs, Gi or Gp but possibly Go.

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A simple experimental index for the evaluation of inotropic responses

Cited by 17 publications

References 18 publications

Reduced cardiotoxicity and increased cytotoxicity in a novel anthracycline analogue, 4′-amino-3′-hydroxy-doxorubicin

Reduced cardiotoxicity and increased cytotoxicity in a novel anthracycline analogue, 4′-amino-3′-hydroxy-doxorubicin

Further Characterization of Nociception-Related and Arterial Pressure-Related Neuronal Responses in the Nucleus Reticularis Gigantocellularis of the Rat

Further Elucidation of a Pertussis Toxin-Sensitive Transmembrane Signaling Mechanism Involved in Central α(2)-Adrenoceptor Activation in the Rat

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