ABSTRACT
AIM: In failing myocardium the mechanical response to beta-adrenoceptor stimulation is attenuated. Alternative signalling systems might provide inotropic support when the beta-adrenoceptor system is dysfunctioning. Accordingly, the inotropic responses to alpha 1- and beta-adrenoceptor stimulation by the endogenous adrenoceptor agonist noradrenaline in non-failing and failing rat hearts were compared. METHODS: Chronic heart failure was induced in male Wistar rats by coronary artery ligation. Corresponding sham groups were prepared. After 6 weeks, papillary muscles from non-failing and failing hearts were isolated. Receptor binding studies were performed in the corresponding myocardium. The alpha 1-adrenoceptor-mediated inotropic response was not changed while the beta-adrenoceptor-mediated response was substantially reduced in failing compared with non-failing myocardium. RESULTS: No change in potency for the agonists was observed at the alpha 1-adrenoceptors, while an increased potency for the agonists at the beta-adrenoceptors was found during heart failure. The lusitropic response to beta-adrenoceptor stimulation was intact during heart failure. No over all change in affinity or number of either adrenoceptor type was observed in receptor binding studies. The alpha 1-adrenoceptor-mediated inotropic response became dominating compared with the beta-adrenoceptor-mediated one in failing rat myocardium in contrast to the dominating role of the latter in non-failing myocardium. The attenuation of the beta-adrenoceptor-mediated inotropic response in rat failing myocardium was not because of a reduced number of receptors. CONCLUSION: Increasing contractility through stimulation of alpha 1-adrenoceptors in situ by the endogenous agonist may be an alternative way of inotropic support during heart failure and even more so during beta-adrenoceptor blockade.
Subject(s)
Adrenergic alpha-Agonists/pharmacology , Heart Failure/physiopathology , Myocardial Contraction/drug effects , Norepinephrine/pharmacology , Receptors, Adrenergic/physiology , Vasoconstrictor Agents/pharmacology , Adrenergic beta-Agonists/pharmacology , Animals , Cardiotonic Agents/pharmacology , Dose-Response Relationship, Drug , Isoproterenol/pharmacology , Male , Phenylephrine/pharmacology , Rats , Rats, Wistar , Receptors, Adrenergic, alpha-1/physiology , Receptors, Adrenergic, beta/physiologyABSTRACT
RATIONALE AND OBJECTIVES: The authors compared the cardiovascular effects of gadodiamide injection and gadopentetate dimeglumine. METHODS: Gadodiamide injection or gadopentetate dimeglumine, each at doses of 0.3 or 1.5 mmol per kilogram of body weight, or saline volume control was administered intravenously in the cephalic vein of anesthetized dogs. Hemodynamic parameters, electrocardiographic parameters, and peripheral flow were measured. RESULTS: Neither the low or high dose of gadodiamide injection caused statistically significant (P < .05) changes in any of the measured cardiovascular parameters. High doses of gadopentetate dimeglumine, however, significantly decreased left ventricular and systemic blood pressure and significantly depressed left ventricular contractility (P < .05). CONCLUSION: Gadodiamide injection caused no observable cardiovascular effects, whereas high doses of gadopentetate dimeglumine caused cardio-depressive and hypotensive effects.
Subject(s)
Contrast Media/toxicity , Gadolinium/toxicity , Hemodynamics/drug effects , Meglumine/toxicity , Organometallic Compounds/toxicity , Pentetic Acid/analogs & derivatives , Animals , Contrast Media/administration & dosage , Dogs , Drug Combinations , Female , Gadolinium/administration & dosage , Gadolinium DTPA , Injections, Intravenous , Male , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Pentetic Acid/administration & dosage , Pentetic Acid/toxicityABSTRACT
This study was designed to compare the cardiac electrophysiology and mechanical effects of iodixanol to those of iotrolan, iopromide, ioxaglate and diatrizoate. Two consecutive injections of contrast media (CM) (0.3 g I/kg and 0.9 g I/kg b.w.) were given to spontaneously beating, Langendorff-perfused rat hearts. CM were given as a single, short-lasting bolus injection (i.e. over 2 and 5 s). Changes in aortic pressure, left ventricular pressures and ECG were continuously recorded during constant volume perfusion. The nonionic CM had less pronounced effects on aortic pressure than had the ionic media. The peak rate of isovolumetric contraction (LV dP/dt(max)) was slightly decreased by iodixanol and iotrolan, slightly more decreased by iopromide and markedly decreased by ioxaglate and diatrizoate. Similarly, the peak rate of pressure decline (LV dP/dt (min)) was only slightly decreased by iodixanol and iotrolan. Also, the 2 nonionic dimers had the smallest effects on the left ventricular end diastolic pressure (LVEDP) and heart rate. Ioxaglate lengthened the PQ-interval, but less so than diatrizoate. THe QT-interval was only slightly lengthened by iodixanol and iotrolan, as compared to the lenghthening caused by iopromide, ioxaglate and diatrizoate. Single ventricular extrasystoles were seen in all groups. Extrasystoles up to 3 coupled beats were registered after ioxaglate and diatrizoate. No episodes of ventricular fibrillation occurred with any CM. In conclusion, the nonionic dimers, and in particular iodixanol, induce only minor changes in cardiac function, whereas the ionic dimer ioxaglate and the ionic monomer diatrizoate induce pronounced effects.
