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Biomedical subjects

H Gelband

Publications and source records attributed to H Gelband.

At least 37 records · Page 2Linked to original sources
PubMed1990

Synergistic hypotensive effect of vasoactive intestinal polypeptide and alpha-blockade with phentolamine. Evidence for vasoactive intestinal peptide alpha-adrenoceptor coupling in the cardiovascular system of newborn dogs.

Vasoactive intestinal polypeptide (VIP) is a neuropeptide with potent circulatory effects in the adult animal and human. Little is known about its effects or mechanism of action in the immature animal. These series of experiments evaluated the effects and possible mechanism of action of VIP on the developing canine cardiovascular system. In all three series, measurements of mean heart rate and blood pressure were taken in the control state, after parasympathetic denervation with bilateral cervical vagotomies, and after autonomic blockade with propranolol (1 mg/kg) and phentolamine (0.5 mg i.v.). In series 1, we characterized the role of alpha-adrenergic receptors in early newborn puppies by investigating the hemodynamic effects of phentolamine alone in five early newborn puppies. In series 2, the hemodynamic effects of intravenous VIP infusion (0.2 microgram/kg/min) were recorded and compared in six early newborn puppies and in 10 late newborn puppies. In series 3, the hemodynamic effects of phentolamine in the presence of VIP receptor binding inhibitor were studied. In early newborn puppies, VIP had essentially no effect on heart rate or blood pressure until phentolamine was given; then, blood pressure decreased by 17% (p less than 0.005). In late newborn puppies, VIP resulted in an increase in heart rate in the control state but not after parasympathetic or sympathetic denervation. In early newborn puppies, phentolamine alone resulted in a 24% decrease (p less than 0.005) in blood pressure, compared with a 54% decrease (p less than 0.005) in early newborn puppies preexposed to VIP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Comparisons of the electrophysiological effects of intravenous sotalol and propranolol on the immature mammalian heart.

Sotalol is a beta blocker that has also been reported to exert class III antiarrhythmic effects. To evaluate the effects of sotalol on the immature heart, and specifically to assess the relative importance of its class III action, the electrophysiologic effects of incremental doses of intravenous dl-sotalol (cumulative dose of 8 mg/kg) were studied in 11 intact canines (ages 4-15 days) utilizing intracardiac programmed stimulation and electrogram recording techniques. These results were compared to the electrophysiologic effects obtained in an additional 14 neonatal canines given 0.6 mg/kg of the beta blocker propranolol intravenously. Sotalol caused a greater increase than propranolol in the resting sinus cycle length (45 vs. 4%). Importantly, sotalol resulted in greater increases in atrial and ventricular muscle refractoriness than did propranolol (AERP--77 vs. 4%, AFRP--57 vs. 6%; VERP--53 vs. 4%, VFRP--51 vs. 7%). Thus, the electrophysiologic effects of sotalol include large changes in myocardial refractoriness that are not observed with simple beta blockade induced by propranolol. These results suggest that sotalol exerts a significant class III effect in the immature mammalian heart, and thus may be useful as an antiarrhythmic agent in the neonate.

Analysis of Variance↗
PubMed1988

Effects of hypoxia on calcium fluxes and force development in the neonatal rat atrium.

The effects of hypoxia on 45calcium fluxes and force development were studied in the resting and stimulated (high potassium/low sodium solutions or Bay K 8644) neonatal rat atrium. Under normoxic conditions, high potassium (100 mmol.litre-1)/low sodium Tyrode solution and Bay K 8644 (2.5 X 10(-5) mol.litre-1) significantly increased calcium uptake above that measured in normal Tyrode solution. High potassium/low sodium Tyrode solution elicited a sustained tonic contracture. Bay K 8644 did not increase resting tension but induced spontaneous phasic contractions in some preparations. Hypoxia failed significantly to alter resting calcium uptake but partially inhibited (50-90%) the high potassium/low sodium and Bay K 8644 induced calcium uptake (that is, the calcium uptake above that measured in normal Tyrode solution). The magnitude of the high potassium/low sodium induced contracture was increased by hypoxia (15 min). Bay K 8644 had no effect on resting tension (in five out of six experiments) after 15 min of hypoxia. Acidosis failed to affect resting (with the exception of the 210 min time point), high potassium/low sodium induced, and Bay K 8644 induced calcium uptakes and had little effect on the high potassium/low sodium induced contracture. It is hypothesised that hypoxia reduces the cells' ability to regulate calcium. Furthermore, it appears that hypoxia's effects on calcium fluxes and the high potassium induced contracture involve other mechanisms besides the associated acidosis.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

The non-catecholamine-mediated electrophysiological effects of intravenous bethanidine sulfate on the immature mammalian heart.

In a preliminary study, we found that bethanidine sulfate had important electrophysiologic effects on the neonatal canine heart, specifically that bethanidine increased atrial effective and functional refractory periods. Other effects (increase in heart rate blood pressure and enhanced atrioventricular conduction) were thought to be due to a release of endogenous catecholamines. To investigate the non-catecholamine-mediated effects of bethanidine, we administered 10 mg/kg i.v. bethanidine to eight neonatal puppies ages 6-14 days pretreated with 0.6 mg/kg of propranolol and compared them with a control group of six neonates that received propranolol followed by a placebo. In the bethanidine group, the mean atrial effective and functional refractory periods increased significantly from 58 to 109 ms and from 108 to 185 ms, respectively (p less than 0.0001). Bethanidine also caused a decrease in resting heart rate (from 154 beats/min postpropranolol to 144 beats/min postbethanidine, p less than 0.002). These effects were not observed in the placebo group. Wenckebach periodicity during incremental atrial pacing did not change significantly. There was a modest increase in the ventricular refractory periods following bethanidine. Thus, the direct electrophysiologic effects of bethanidine in the neonate include a significant prolongation of atrial refractoriness and a decrease in sinus node automaticity. Ventricular refractory periods, while increased, did not show the dramatic prolongation exhibited by the atrium. The atrial specificity of bethanidine is unique and may prove useful in the treatment of supraventricular arrhythmias in the neonatal period.

Animals↗
PubMed1988

Electrophysiologic and hemodynamic effects of bethanidine sulfate on the immature mammalian heart.

The cumulative electrophysiologic and hemodynamic effects of bethanidine sulfate (2.5, 5, 10 and 15 mg/kg i.v.) were studied in 9 canine neonates and 7 adult dogs. Increased heart rate, blood pressure and enhanced atrioventricular nodal function, observed in both groups, and decreased ventricular refractory periods and inducibility of ventricular arrhythmias seen in the adult, are probably related to a bethanidine-mediated release of catecholamines. However, in spite of the catecholamine release, bethanidine sulfate results in a significant prolongation of atrial refractoriness, this effect being quantitatively more important in the neonate than in the adult.

Aging↗
PubMed1988

Atrioventricular nodal function in the immature canine heart [corrected and republished article orginally printed in Pediatr Res 1987 Nov;22(5):616-20].

Previous studies have suggested that the atrioventricular nodal functional refractory period in the neonate is equal to or shorter than that of the ventricle, providing little or no protection to the ventricle against rapid atrial rates and allowing closely coupled atrial beats to fall within the ventricular vulnerable period. We evaluated atrioventricular node function in 21 mongrel neonatal puppies, 3-15 days old, and 15 adult dogs utilizing intracardiac His bundle recording and stimulation techniques. The mean atrioventricular nodal functional refractory period (173.1 +/- 20.0 ms) exceeded both the ventricular effective refractory period (139.5 +/- 14.3) and ventricular functional refractory period (163.3 +/- 14.5) in the neonates. Furthermore, the atrioventricular node was the site of limiting antegrade conduction in all neonates. No ventricular arrhythmias were induced by atrial extrastimulation in any of the neonates. The site of conduction delay during atrial extrastimulation was confined to the atrioventricular node in 15/16 neonates (94%) while 1/16 (6%) had combined nodal and infranodal delay. The neonates developed Wenckebach, at significantly faster heart rates than the adults, but both groups developed Wenckebach at approximately twice the resting heart rate. Retrograde conduction was a consistent finding in the neonates. However, antegrade Wenckebach occurred at a significantly faster heart rate than retrograde Wenckebach suggesting different functional properties. Our data suggest that in the neonatal canine, the atrioventricular node functional refractory period is longer than both the ventricular effective refractory period and ventricular functional refractory period. Furthermore, the degree of protection offered by the neonatal atrioventricular node to the ventricle appears to be comparable to that of the adult.

Animals↗
PubMed1988

In vivo demonstration of maturational changes of the chronotropic response to alpha-adrenergic stimulation.

In vitro studies suggest that neonates and adults may have different cardiac chronotropic responses to alpha-adrenergic stimulation. To investigate these differences in vivo, three groups of dogs were studied. Group I = 12 puppies, ages 3-7 days; group II = 12 puppies ages 8-15 days, and group III = seven adult dogs. Heart rate and blood pressure determinations were made in the control setting and then after combined beta-adrenergic and parasympathetic blockade (propranolol 0.6 mg/kg and bilateral vagotomies). Alpha-stimulation was then achieved with phenylephrine given in doses of 0.5, 1.0, and 10.0 micrograms/kg/min. A second, high dose of propranolol (1.0 mg/kg intravenously) was administered after the highest phenylephrine infusion dosage to assure complete beta-blockade. Finally, alpha-blockade was achieved with phentolamine (groups I and II: 0.5 mg intravenously; group III: 5.0 mg intravenously). An alpha-mediated positive chronotropic effect was observed in 42 and 100% of subjects in groups I and II, respectively, but never observed in the adults. Whereas alpha-blockade with phentolamine resulted in a large decrease in heart rate of all puppies (groups I and II), it had no effect on adults. Blood pressure responses were similar in all three groups. Thus, there are important maturational changes in the chronotropic response to alpha-adrenergic stimulation and blockade demonstrable in the intact neonatal canine.

Aging↗
PubMed1987

Reverse alternating Wenckebach periodicity.

An atrial pacing-induced reverse conduction pattern of the alternating Wenckebach periodicity was observed in 5 of 42 children (12%) during electrophysiologic study. This conduction pattern is a reverse of the usual alternating Wenckebach periodicity: During an underlying 2:1 atrioventricular conduction block there is progressive shortening of the conduction time of the conducted impulses with termination in a lower degree of block. This reverse alternating Wenckebach periodicity may be caused by a mechanism similar to that in other Wenckebach phenomena.

Atrioventricular Node↗
PubMed1987

Calcium fluxes in the neonatal canine myocardium: the effects of isoproterenol and electrical stimulation.

Ca2+ uptake into and the Ca2+ content of both resting and stimulated neonatal canine left ventricular muscle strips were studied with 45Ca2+. The characteristics of the total tissue Ca2+ exchange were defined by allowing 45Ca2+ to efflux from 45Ca2+ equilibrated muscle into ice-cold (4 degrees C) modified Tyrode's solution. The resulting 45Ca2+ efflux curve could be described using a three-compartment model. These compartments were designated as rapid, intermediate and slow on the basis of their half-times (t1/2) for exchange. The t1/2 for the exchange of Ca2+ within the slow compartment at 4 degrees C was 103.1 +/- 7.0 min. The physiological characteristics of the slow compartment were investigated by performing experiments at 37 degrees C and then allowing tissues to efflux at 4 degrees C as described above. The uptake of Ca2+ into the slow compartment at 37 degrees C consisted of an initial rapid uptake (t1/2 approximately 1.6 min) followed by a slower prolonged uptake (t1/2 approximately 54 min), indicating the presence of a nonhomogeneous compartment. The observations that the t1/2 for exchange of the slow compartment was shorter at 37 degrees C than at 4 degrees C, and that its Ca2+ content was significantly increased by isoproterenol (10(-6) M), suggests that the slow compartment is of intracellular origin. A single suprathreshold electrical stimulus, to elicit an action potential, caused a significant decrease (approximately 350 mumol/kg; p less than 0.01) in the Ca2+ content of the slow compartment, consistent with the view that Ca2+ sites within this compartment play a significant role in the excitation-contraction coupling process.

Action Potentials↗
PubMed1987

The electrophysiologic effects of propafenone hydrochloride in the neonatal canine.

The electrophysiologic effects of the new antiarrhythmic agent, propafenone, were investigated in 10 mongrel canine neonates, ages 5 to 11 days. Utilizing standard His bundle recording and stimulation techniques, assessments of sinus and atrioventricular (AV) node function and atrial, AV nodal, and ventricular refractory periods were performed prior to (control) and after cumulative intravenous doses of 1, 2, and 4 mg/kg of propafenone. Propafenone depressed the spontaneous heart rate and prolonged the postatrial pacing recovery times. AV nodal function was depressed as manifested by Wenckebach periodicity occurring at slower pacing rates, increases in AV nodal conduction time, and increases in AV nodal refractoriness. Atrial and ventricular refractory periods were prolonged significantly in a dose-dependent fashion. Prolongation of the His-Purkinje conduction time occurred at the highest dose. Thus, propafenone exerts a generalized depressant effect on neonatal myocardial conduction and refractoriness which suggests that this agent may be useful in the therapy of atrial and ventricular dysrhythmias in the immature heart.

Animals↗
PubMed1986

Application of the Rosenblueth hypothesis to assess atrioventricular nodal behavior.

Based on the Rosenblueth hypothesis, atrioventricular nodal behavior is evaluated using a method involving the coupling interval at the level of the atrioventricular nodal step delay. If the sum of the coupling interval at the level of step delay and the resultant step delay is greater than the atrial coupling interval, Wenckebach periodicity results; if the sum is less than the atrial coupling interval, the reverse Wenckebach phenomenon occurs; and if both are equal, steady state conduction is reached.

Atrioventricular Node↗
PubMed1986

Atrial pacing-induced alternating Wenckebach periodicity and multilevel conduction block in children.

Multilevel block within the atrioventricular (AV) node has not been previously described in children. Six children with atrial pacing-induced repetitive block are presented. The conduction patterns satisfy the requisites for alternating Wenckebach periodicity or multilevel AV block. In 2 patients the block is documented in the AV node and infra-His region. In 4 patients multilevel block within the AV node is postulated by deductive reasoning. In this study, 2 patterns of alternating Wenckebach periodicity are reported for the first time: sequences of 3:1 block with progressive prolongation of the conducted impulses terminating in 4:1 block; and sequences of 2:1 block with progressive prolongation of the conducted impulses terminating in 2 series of 3:1 block, in which the first conducted impulse following the first 2 blocked beats is not the shortest one, whereas that following the second 2 blocked beats is the shortest.

Atrioventricular Node↗
PubMed1986

Application of the Rosenblueth hypothesis to assess cycle length effects on the refractoriness of the atrioventricular node.

In adults, the effective refractory period of the atrioventricular (AV) node is lengthened, whereas that of the atrium, His-Purkinje system or ventricular myocardium is shortened with a shorter atrial pacing cycle length. However, in children, the effective refractory period of the AV node at shorter cycle lengths is also shortened. Based on Rosenblueth's 1-step delay hypothesis, an index of refractoriness within the AV node is defined as the longest coupling interval at the level of step delay within the AV node of an impulse that cannot be conducted to the His bundle. The slopes relating cycle length and refractoriness of the AV node are determined by both the conventional and revised methods in 9 pediatric patients with heart disease. The slope is positive for all patients using the revised method. The difference in values between the 2 methods in older children is striking because the slope is converted from a negative to a positive value. It is concluded that the AV node has the same positive slope relating cycle length and refractoriness as other cardiac tissues.

Adolescent↗
PubMed1986

Digoxin-quinidine interaction in the neonatal dog.

The effects of quinidine on steady state serum and tissue digoxin concentrations in the neonatal dog were studied. To determine the effects of quinidine on serum digoxin concentrations, two groups of neonates were evaluated: Group I (n = 11) was digitalized with 40 micrograms/kg body weight, intramuscularly, and placed on a 10 micrograms/kg per day maintenance dose; Group II (n = 7) was digitalized with 50 micrograms/kg per day, intraperitoneally, and placed on a 20 micrograms/kg per day maintenance dose. After 10 days of digoxin alone, quinidine was coadministered (30 mg/kg per day, intraperitoneally) for 7 days. Serum digoxin concentrations were measured before quinidine and 1, 3 and 7 days after combined digoxin-quinidine therapy. In Group I, the control serum digoxin concentration was 1.38 +/- 0.32 ng/ml and after 7 days of combined therapy it was unchanged (1.39 +/- 0.31 ng/ml). In Group II, the control serum digoxin concentration measured 2.80 +/- 0.49 ng/ml and after 7 days of combined therapy it, too, was unchanged (3.10 +/- 0.65 ng/ml). The effects of combined digoxin-quinidine administration on tissue digoxin concentrations were studied in two other groups of neonates. Group III (n = 6) was given a low maintenance dose of digoxin (10 micrograms/kg per day, intramuscularly) and a full 7 days of coadministered quinidine; in Group IV (n = 6), digoxin was given at a higher dose (20 micrograms/kg per day, intraperitoneally) and a shorter duration of combined digoxin-quinidine therapy (3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Atrial vulnerability in the immature canine heart.

The induction of repetitive atrial responses during atrial extrastimulation (atrial vulnerability) was studied in 3 groups of dogs. Group I consisted of 19 neonatal puppies (age 3 to 15 days), group II of 10 older puppies (age 5 to 11 weeks) and group III of 10 adult dogs. In all dogs, atrial extrastimulation was performed coupled to a constant paced rhythm that was 85 +/- 7% of the sinus cycle length at rest in group I, 86 +/- 6% in group II and 83 +/- 10% in group III. In all groups, atrial repetitive responses were observed as the atrial functional refractory periods were approached during extrastimulation; however, the number of repetitive atrial responses was greater and the duration of repetitive firing longer in the neonates. In the neonatal group as many as 28 repetitive atrial responses were induced (9.4 +/- 8.2 beats) and the duration of repetitive atrial firing averaged 838 ms (range 120 to 2,425). In contrast, in only 1 of 20 older puppies and adult dogs were more than 2 repetitive atrial beats observed (number of repetitive atrial beats in group II, 1.7 +/- 1; in group III, 1.2 +/- 0.5). Thus, the normal neonatal atrium is more susceptible to intraatrial reentry in response to premature extrastimulation than the more mature canine atrium. This enhanced atrial vulnerability may be related to the shorter atrial refractory periods of the neonate and may be of importance in understanding the genesis of certain dysrhythmias in the human neonate.

Aging↗
PubMed1985

The effect of high K+ depolarization and verapamil on 45Ca2+ fluxes in the canine myocardium.

The effects of high K+ depolarization and verapamil on Ca2+ uptake and the total intracellular Ca2+ content of canine ventricular muscle strips (approximately 0.5 mm thick) were investigated. High K+ (96 mM) increased Ca2+ uptake above control and maintained this enhanced uptake throughout a 90 second measuring period. Verapamil (5 X 10(-6) M) significantly (p less than 0.05) inhibited this high K+ stimulated uptake. However, verapamil (5 X 10(-6) M) also had a direct effect on Ca2+ fluxes, causing a significant increase in both Ca2+ uptake (p less than 0.001) and total intracellular Ca2+ content (p less than 0.001) in the resting tissue. Therefore, verapamil's apparent inhibition of high K+ stimulated Ca2+ uptake may have resulted from some mechanism other than Ca2+ channel blockade.

Animals↗