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R D Tanz

Publications and source records attributed to R D Tanz.

At least 19 recordsLinked to original sources
PubMed1991

[Enhanced myocardial depression from bupivacaine in diabetic rats].

We examined the direct effects of bupivacaine on the diabetic rat myocardium using an isolated perfused (Langendorff) heart preparation. Rats were made diabetic by injection of streptozotocin (55 mg.kg-1, i. v.). 12 weeks after the administration of streptozotocin, hearts were excised and perfused using Langendorff technique. Following 60 min for equilibration, diabetic hearts from the 12-week animals exhibited significant bradycardia. Bupivacaine 3 mcg.ml-1 did not decrease myocardial contractility in control animals. However, 3 mcg.ml-1 bupivacaine decreased contractility significantly in diabetic animals at nearly all periods. Bupivacaine decreased heart rate and coronary flow significantly and similarly in control and diabetic rats hearts. After pacing at 4 Hz, bupivacaine decreased contractility more in diabetic group than in control group. These results indicate that the presence of a diabetic state appears to enhance the sensitivity of the heart to the myocardial depressant effect of bupivacaine.

Animals↗
PubMed1989

Histamine relaxation of aortic rings from diabetic rats.

The effect of histamine-induced relaxation on thoracic aortic rings from rats 5, 12, 24 and 52 weeks following streptozotocin-induced diabetes was determined. Preliminary studies confirmed the dependence of histamine-induced relaxation and the independence of nitroglycerin-relaxation (GTN) on the presence of endothelium (EDRF). Diabetes was confirmed by blood glucose levels exceeding 300 mg/dl. Rings with endothelium were depolarized several times with 50 mM KCL and then contracted with phenylephrine (10(-6)). Dose-response curves were plotted from data obtained following exposure to histamine (10(-7)-10(-3)) and GTN (10(-9)-10(-7)) and compared to responses from age-matched untreated controls, diabetic and diabetic rats treated with insulin (2 U/day). The relaxation produced by histamine on phenylephrine pre-contracted rings was similar in all three groups from 5-week age matched rats. However, histamine-induced relaxation from untreated diabetic rats was significantly depressed at 12, 24 and 52 weeks (p less than 0.001). Conversely there was no difference in the relaxation elicited by GTN on rings obtained from the three groups at any age. Pretreatment with diphenhydramine (5 x 10(-7)) on aortic rings from 12 and 52-week age matched rats resulted in qualitatively similar histamine dose-response curves that were displaced about two orders of magnitude to the right, indicative of H1 receptor competitive antagonism. These results demonstrate that the duration of diabetes alters the responsiveness of rat thoracic aortic rings to histamine but not to GTN and suggests that the responses elicited by certain agonists on target tissues may be significantly altered depending on the duration of diabetes.

Animals↗
PubMed1989

Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats.

1. Isolated hearts perfused by the method of Langendorff from 6, 12 and 24 week streptozotocin (STZ) diabetic rats displayed a significant bradycardia following 60 min equilibration. The rate of hearts from 12-week diabetic rats (164 +/- 17) displayed the greatest bradycardia compared to age-matched controls (268 +/- 15; P less than 0.001), and diabetics treated with insulin (232 +/- 17; P less than 0.01), but by 52 weeks the heart rate of the 3 groups was similar. With advancing age the effect of STZ diabetes on the rate of rat isolated perfused hearts remained unchanged but the rate of the control and diabetic + insulin groups declined. 2. Hearts from 6-52 week STZ-treated rats were found to be more sensitive to the negative chronotropic effect of methacholine, the greatest difference occurring in hearts from the 12 week animals. Atropine (10(-7) M) did not affect the resting heart rate of age-matched controls or diabetics but blocked methacholine (2.6 x 10(-6) M)-induced bradycardia in both, suggesting that the site of action of diabetic bradycardia is not the muscarinic receptors. 3. At the end of equilibration there was a significant decrease in coronary flow in hearts from 12 week diabetic animals. In spontaneously beating diabetic rat hearts administration of methacholine (2.6 x 10(-6) M) produced a significantly greater decrease in coronary flow in the 12, 24 and 52 week diabetic hearts. When electrically paced (5 Hz) however, there was no difference in response to methacholine between the three groups except at 52 weeks between the age-matched control and diabetic groups. This suggests that the more pronounced reduction induced by methacholine on the coronary flow of diabetic hearts is secondary to its negative chronotropic effect. 4. In general, hearts from diabetic animals treated with insulin respond similarly to their agematched controls in the presence and absence of methacholine.

Aging↗
PubMed1985

Insurmountable antagonism of ouabain-induced coronary constriction by prazosin.

A linear dose-response curve was produced by the addition of ouabain (10(-8)-10(-6) M) to the media bathing segments of porcine right coronary arteries. A concentration of 10(-6) M ouabain produced constriction equal to 47% of that resulting from exposure to 35 mM KCl. The ouabain dose-response curve was competitively displaced one order of magnitude by the previous addition of verapamil (2.2 X 10(-8) M), and non-competitively by the prior exposure to prazosin (6.5 X 10(-7)-6.5 X 10(-13) M). The inhibitory effect of prazosin appears to be unrelated to its alpha 1-adrenergic blocking action.

Animals↗
PubMed1985

The effect of calcium on cardiac anaphylaxis in guinea-pig Langendorff heart preparations.

This study was designed to determine the effects of different calcium concentrations on the perfused isolated guinea-pig heart preparation subjected to cardiac anaphylaxis. Following challenge both physiological and biochemical effects were determined on hearts from guinea-pigs previously sensitized to ovalbumin. Perfusion media containing either 1,2.54 or 5 mM of calcium was used. In comparison to nonsensitized controls challenged to ovalbumin, challenged sensitized hearts (CSH) perfused with 1 mM Ca2+ showed an initial increase in dF/dt, a prolonged rise in H.R. and depressed coronary flow. Raising the calcium concentration to either 2.54 or 5 mM in CSH preparations resulted in a marked increase in the release of lactate dehydrogenase (LDH) into the coronary effluent and depressed coronary flow. Perfusing CSH preparations with increasingly higher calcium concentrations more often produced severe tachyarrhythmias and fibrillation. The highest level of histamine released into the coronary effluent occurred immediately following challenge and then declined exponentially over the next 20 min. Both challenge and the administration of histamine induced an immediate but transient increase in H.R., a rise in dF/dt, and LDH release. The infusion of histamine produced an increase in coronary flow, but on porcine tubular coronary arterial segments only a direct constricting effect was obtained. The prior administration of cimetidine (10(-5) M) attenuated the rise in LDH and dF/dt in CSH and nonsensitized preparations infused with histamine (3 micrograms). However, although cimetidine did not affect the decreased coronary flow in CSH preparations, it initially attenuated the rise in coronary flow in preparations infused with histamine. These results suggest that calcium enhances the likelihood of tachyarrhythmias in cardiac anaphylaxis. The release of LDH in histamine-infused preparations and those CSH preparations perfused with 2.54 and 5 mM calcium-containing media also suggests the possibility that calcium enhances the damaging effects on the myocardial cell in cardiac anaphylaxis.

Anaphylaxis↗
PubMed1984

Electromechanical dissociation and possible uncoupling of phosphorylation following tachydysrhythmogenic dose of amrinone in the guinea-pig Langendorff heart preparation.

In the guinea-pig Langendorff heart preparation amrinone induced tachydysrhythmia and electromechanical dissociation at 1000 micrograms/ml but not at 50 and 250 micrograms/ml. At 1000 micrograms/ml, the myocardial oxygen consumption was twice the value at equilibration in spite of a very marked fall in contractile force, thus suggesting that amrinone at that toxic dose level uncoupled phosphorylation. Amrinone at 50 and 250 micrograms/ml caused a dose-related reversal of the cardiac depressant effect induced by verapamil suggesting, therefore, that the positive inotropic effect is due at least in part to influx of Ca2+ into the sarcoplasm. It is suggested that the electromechanical dissociation and the possible uncoupling of phosphorylation induced by a toxic dose of amrinone are related to a considerable influx of Ca2+ into the sarcoplasm and the mitochondria.

Aminopyridines↗
PubMed1984

Comparative cardiotoxicity of bupivacaine and lidocaine in the isolated perfused mammalian heart.

This study was designed to compare the direct actions of bupivacaine and lidocaine on the isolated perfused guinea pig Langendorff heart preparation. Sixty min after mounting, either bupivacaine HCl (0.3 or 3 micrograms/ml) or lidocaine HCl (10 or 30 micrograms/ml) was added to the perfusate, and the effect (if any) was compared to untreated control values 30, 60, and 90 min later. Although the highest concentrations of both drugs invariably produced statistically significant reductions in heart rate, df/dt, coronary blood flow, and myocardial oxygen consumption (MVO2), these reductions were consistently greater after bupivacaine. Moreover, arrhythmias occurred in 6 of 12 preparations in those hearts exposed to 3 micrograms/ml of bupivacaine. Most often these arrhythmias consisted of heart block and bi- or trigeminy. Additional studies indicated that the reduction in coronary blood flow and MVO2 produced by 3 micrograms/ml of bupivacaine was a consequence of its direct negative inotropic and chronotropic action. Although the myocardial depression produced by bupivacaine and lidocaine could be reversed readily by substituting fresh perfusate, increasing the extracellular calcium concentration in stepwise increments did not augment the negative inotropic or chronotropic effect produced by 3 micrograms/ml of bupivacaine or 10 micrograms/ml of lidocaine. We conclude that 3 micrograms/ml of unbound bupivacaine is more cardiotoxic than 30 micrograms/ml of unbound lidocaine in this model.

Animals↗
PubMed1983

Mechanism of cardiac glycoside-induced toxicity: physiology, biochemistry, and electron microscopy.

The addition of an arrhythmogenic concentration of ouabain (1.37 X 10(-6) M) results in a number of physiological, biochemical, and ultrastructural changes in isolated perfused guinea pig (Langendorff) heart preparations. Chronologically the following alterations occurred: first, a transient rise in ventricular cyclic AMP followed by a reduction in ventricular ATP, relatively minor electrocardiograph abnormalities (e.g., occasional missed beats, transient episodes of tachycardia, and occasional premature ventricular contractions), and a significant decline in coronary flow. A short time later, preparations became tachycardic and within 10 min asystole supervened. Simultaneously with the occurrence of tachyarrhythmias, there was a significant increase in the release of creatine kinase and lactate dehydrogenase into the coronary effluent. Ultrastructural analysis of the ventricular endocardium revealed marked alterations in the mitochondria, disappearance of cytosolic glycogen granules, and chromatin clumping in the nuclei. Pretreatment with d,l-propranolol (3.38 X 10(-6) M) 15 min before ouabain abolished alterations caused by ouabain alone. Studies where ouabain-treated hearts were paced or coronary flow maintained suggest that changes in neither heart rate nor coronary flow are responsible for the protective action of propranolol. Results obtained indicate that ouabain-induced toxicity may in part result from an increase in coronary resistance producing myocardial hypoxia, cell damage, and arrhythmias. Preliminary studies suggest that the membrane-stabilizing action of propranolol appears to be the basis of its protective effect.

Animals↗
PubMed1983

Electrocardiographic changes induced by amrinone in the isolated perfused guinea-pig Langendorff heart preparation.

ECG changes induced by three different concentrations of amrinone were determined in the spontaneously beating guinea-pig Langendorff heart preparation. At a concentration of 50 micrograms/ml, there were no ECG changes except for a sinus tachycardia having a mean increase of 15.64 +/- 4.0, (P less than 0.01). At a concentration of 250 micrograms/ml, sinus tachycardia was more evident (+ 20.86% +/- 1.22; P less than 0.001). There was also a statistically significant shortening of the Q-T interval (P less than 0.001). With 1000 micrograms/ml, amrinone further increased heart rate (+ 45.10% +/- 13.26; P less than 0.001). There was a greater shortening of the Q-T interval, and occasionally sagging of the S-T segment. Dysrhythmic phenomena including coupled beats, at times with R waves appearing during the vulnerable period of the T wave; ventricular premature beats and alternating polymorphic ECG patterns, were evident. Second and third degree atrioventricular block preceded by marked prolongation of the P-R interval less commonly developed at this concentration. On the basis of these observations and others, it appears that as regards the development of cardiotoxocity, amrinone possesses a relatively wide margin of safety not less than 5 and may even approach 20.

Aminopyridines↗
PubMed1977

Reversal of aconitine-induced tachycardia by prostaglandins in the rabbit Langendorff preparation.

The ability of PGA2, E1, E2, and F2alpha to alter: (a) the refractory period (as judged by the maximal driving frequency); (b) the rate of automatically beating aconitine-treated papillary muscles; and (c) the rate of both untreated and aconitine-treated Langendorff preparations, was studied. The addition of PGA2 (3.0 mumol), PGE2 (2.84 mumol), and PGF2alpha (2.1 mumol) to the perfusate returned heart rate to pre-aconitine levels in the Langendorff preparation, but this action was frequently accompanied by atrioventricular dissociation. In contrast, PGE1 (2.82 mumol) was ineffective in antagonising aconitine-induced tachycardia. In the normally beating rabbit Langendorff, PGF2alpha (2.1 mumol) produced a slight but statistically significant negative chronotropic effect. Neither cardiac contractile force nor maximal driving frequency was altered by the addition of prostaglandins. These results suggest that PGA2, PGE2, and especially PGF2alpha may exert antiarrhythmic activity by direct action(s) upon in vitro rabbit myocardial preparations.

Aconitine↗