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D V Priola

Publications and source records attributed to D V Priola.

At least 19 recordsLinked to original sources
PubMed1999

Shortening deactivation of cardiac muscle: physiological mechanisms and clinical implications.

UNLABELLED: PHYSIOLOGICAL MECHANISM: A rapid change of length applied during isometric contraction of skeletal or cardiac muscle may result in redeveloped tension less than appropriate for the new length because of "deactivation" of the contractile system. The amount of shortening deactivation is directly related to both the time during the contraction when the length change occurs and to the extent of muscle shortening. If the muscle is permitted to shorten early in the contraction, the redeveloped tension will be appropriate to the new length as predicted from the classic Frank-Starling relationship. However, the same length change, which is imposed later in the contraction, results in a redeveloped tension that is less than predicted. Furthermore, a greater change in length results in less tension being redeveloped than if a smaller length decrement is applied at the same time during the contraction. It has been demonstrated that the reduced tension during active muscle shortening is associated with reduced affinity of troponin C for Ca2+. The free Ca2+ is then picked up by the SR, with less Ca2+ available for tension development until the subsequent contraction. CLINICAL SIGNIFICANCE: Although the clinical significance of shortening deactivation remains speculative, it seems likely that in the intact heart deactivation would affect myocardial O2 consumption. The decreased efficiency with which the heart maintains a given stroke work against a high afterload might be related to the lesser degree of fiber shortening and, therefore, less shortening deactivation. Conversely, it is well-known that the same level of stroke work accomplished by an increase in end-diastolic volume requires much less O2. This may be related, at least in part, to the greater degree of shortening with an accompanying increase in deactivation under the latter conditions. For example, in congestive heart failure where ejection fraction and fiber shortening are minimal, the maintenance of the longer fiber lengths could significantly increase the MVO2. Ford has suggested that the deactivating effect of shortening produced by afterload reduction would limit energy expenditure, therefore, exerting a favorable effect on the failing myocardium. It would also seem that an inotropic agent that increased shortening deactivation might compensate for the increased MVO2 caused by the inotrope and have a favorable effect on cardiac work. From most of the studies we have reviewed, it appears likely that shortening deactivation acts as a physiological "feedback" mechanism that affects afterload and in turn, myocardial oxygen consumption. Pathological situations such as acidosis and ischemia have been associated with reduced myofilament Ca2+ sensitivity or affinity and depressed cardiac contractility. Is it then possible that interventions that increase Ca2+ sensitivity might favorably alter ventricular pressure-volume relations during ejection and improve myocardial function by reducing the magnitude of shortening deactivation? Whatever the mechanism and clinical significance, future investigations will help to define the role of shortening deactivation in modifying ventricular function.

Animals↗
PubMed1998

Intrinsic neural regulation of the heart in the chronic, conscious dog.

The present experiments were performed to examine the capability of the intrinsic cardiac nerves (ICN) to modify cardiac performance in the resting chronic, conscious dog. Control and cardiac-denervated dogs were instrumented for recording of left atrial (LA) and ventricular (LV) contractility, heart rate, and atrioventricular (AV) conduction time. Acetylcholine (ACh) and nicotine (Nic) were administered via an indwelling coronary artery catheter. Limited distribution from the injection site only allowed access to the LA, LV, and AV node. Both beta-blockade with timolol and cardiac denervation were used to separate direct effects of ICN stimulation from indirect (e.g., reflex) effects. ACh produced the expected negative inotropic and dromotropic changes. ICN stimulation with Nic caused large decreases in LA on but only trivial effects on the LV. We concluded that the ICN has limited effects on cardiac performance in the resting animal under minimal sympathetic drive. It is likely, however, that the ICN is capable of significantly depressing cardiac function under conditions of elevated sympathetic tone as would be encountered in exercise.

Acetylcholine↗
PubMed1994

Modulation of autonomic responses in normal and denervated isolated canine atria by substance P.

The experiments were performed to determine whether the neuromodulatory effect of substance P (SP) could be demonstrated in the isolated atrium. Strips from the right (RA) and left atria (LA) of normal (control) and denervated canine hearts were placed in an isolated muscle bath, and isometric muscle tension was measured. Inotropic responses to direct muscarinic stimulation were obtained with 1 x 10(-9) to 1 x 10(-8) M acetylcholine (ACh), and responses to stimulation of the intramyocardial intrinsic cardiac nerves (ICN) were produced with nicotine (Nic), 1.0-10 x 10(-6) M. The same drugs were tested in the presence of 1 x 10(-6) M SP, which had no significant inotropic effects of its own. Responses to ACh were unaffected by SP. The primary negative inotropic response to Nic was greatly attenuated by SP in both control and denervated atria, whereas the secondary positive response in control atria was unaffected. This inhibition was very pronounced in LA but less so in the RA. We conclude that SP appears to modulate the responses of the ICN to nicotinic stimulation in a manner similar to that previously observed in intact animals. This mechanism may provide a means of direct modification of efferent cardiac responses by afferent nerves within the heart itself.

Acetylcholine↗
PubMed1992

Tachyphylaxis of the intrinsic cardiac nerves to nicotine: effects on A-V nodal conduction.

1. The possibility that responses of the intrinsic cardiac nerves (ICN) of the dog to nicotinic stimulation are influenced by tachyphylaxis to repeated administration of nicotine (NIC) was evaluated in an anaesthetized preparation. Prolongation of A-V conduction was used as an index of ICN responsiveness. 2. Twenty dogs were placed on cardiopulmonary bypass and an electrode was sutured over the His bundle. Both vagi were sectioned, beta-adrenoceptor blockade instituted, and the hearts were paced. Nicotine (2-100 micrograms) was administered directly into the coronary circulation via an aortic catheter. Tachyphylaxis was estimated from the rate of deterioration of negative dromotropic effect of NIC in response to various protocols of repeated doses. 3. Tachyphylaxis was not observed in response to repeated doses of acetylcholine. 4. Tachyphylaxis to nicotine was found to be both time- and dose-dependent; i.e. increasing the dose or decreasing the time between doses to less than 3 min augmented its development. 5. Tachyphylaxis was pronounced after 5 x 100 micrograms doses of NIC, even if the test doses were greater than 3 min apart and 20 min was allowed to elapse between the two series of test doses. 6. These data are descriptive in nature and no mechanism for the tachyphylaxis could be deduced. Pharmacokinetic data of this nature have not been previously reported for nicotinic stimulation of the intrinsic parasympathetic ganglia of the canine heart. Tachyphylaxis can be avoided when testing the intrinsic innervation of the canine heart if the doses used are less than 100 micrograms and are administered at least 3 min apart.

Acetylcholine↗
PubMed1992

Mechanical properties of the canine mitral valve: effects of autonomic stimulation.

Experiments were designed to determine whether the canine mitral valve actively contracts and, if so, if its mechanical activity can be modulated by the autonomic nervous system. A miniature displacement gauge was sutured to the atrial (muscular) surface of the septal leaflet in 65 dogs under pentothal sodium anesthesia during total cardiopulmonary bypass. During bypass, with blood constantly drained from the left ventricle (LV), the leaflet deflected into the LV during ventricular systole as would be expected with active contraction. With blood present in the LV, leaflet deflection was reversed, indicating a passive displacement. After application of 85% phenol to the atrial surface, ventricular displacement of the leaflet was abolished, whereas the atrial displacement was significantly augmented. There was a positive inotropic effect during sympathetic stimulation and a negative inotropic effect with parasympathetic stimulation, i.e., increased and decreased ventricular deflection, respectively. These effects of autonomic stimulation were abolished by application of phenol to the leaflet muscle. During simultaneous electrical and mechanical recordings from the valve, activation appeared to originate from the atrium, before ventricular depolarization. It was concluded that the valvular muscle actively contracts to assist in bringing the valve leaflets into early apposition. This contraction imparts a measurable level of active "stiffness" to the valve, reducing atrial displacement during ventricular systole. This "stiffness" can be modified by autonomic input and may contribute to dysfunction of morphologically normal mitral valves.

Animals↗
PubMed1992

Substance P modulates autonomic nerve activity in canine hearts.

We examined the hypothesis that substance P (SP) acts as an "afferent neuromodulator" in the heart regulating the response of the cardiac autonomic nerves to reflexes originating in the heart. We employed the acute, isovolumic canine heart preparation in which the amplitude of the chamber pressure accurately reflects changes in contractility. The heart was decentralized except for one-half of the right vagus, which was left intact to permit afferent communication with the central nervous system, while the remaining one-half was tightly ligated so that the distal part could be used for efferent stimulation. SP was injected in doses of 2-10 micrograms ic. There were no significant inotropic responses to 2 and 5 micrograms SP, whereas 10 micrograms produced positive inotropy of 5-15%. When vagal tone was elevated with sustained vagal stimulation, the same doses of SP increased contractility by 12-28%. Similarly, during right stellate ganglion stimulation (SS), SP decreased contractility 8-22%. After the intact half of the right vagus was sectioned, SP modulation of vagal responses was unaffected, while modulation of atrial, but not ventricular, responses to SS was significantly attenuated. When tested on a series of cardiac-denervated dogs, SP had no effect on cardiac inotropy at any dose. However, when contractility was increased with isoproterenol infusion, SP caused a small decrease in ventricular contractility. These results suggest that SP acts as a modulator of cardiac autonomic neural tone. It is possible that the neuropeptide is released from intramyocardial afferent collateral fibers and inhibits the elevation in vagal or sympathetic nerve activity initiated by activation of cardiac primary afferent nerves.

Animals↗
PubMed1990

Effects of histamine on atrial and ventricular contractility in the canine isovolumic heart.

The effects of intracoronary administration of histamine on atrial and ventricular contractility were determined in a paced canine isovolumic heart preparation. Contractility was assessed by recording the pressure developed in saline-filled balloons placed in each of the four cardiac chambers. At doses above 0.1 mg and up to 100 mg histamine produced dose-related positive inotropic responses in all chambers. These were preceded by transient negative effects. The positive responses were not affected by a combination of H1 and H2 receptor antagonists antazoline and cimetidine but were almost completely abolished by the beta adrenoceptor blocker timolol. The negative responses were uninfluenced by either treatment. It was concluded that, in the canine isovolumic heart not subjected to complicating chronotropic and extracardiac factors, moderate doses of histamine are devoid of inotropic effects. Higher doses do produce myocardial stimulation, not mediated by histamine receptors, but probably due to norepinephrine release. These responses are preceded by transient non-specific depressant effects.

Animals↗
PubMed1989

Enhanced acetylcholine release from denervated atria: intrinsic neural supersensitivity.

Atrial tissue from denervated dog hearts was incubated with [3H]choline. When compared with controls, nicotine released more acetylcholine (ACh) from denervated atria at 10(-5) and 2 x 10(-5) M, but not at 5 x 10(-5) M. In parallel contractility studies using tissue from these same atria, the negative inotropic response to nicotine was enhanced at 5 x 10(-6) and 10(-5) M, but not at 2 x 10(-5) or 5 x 10(-5) M nicotine. These results indicate that denervation (i.e. decentralization) supersensitivity of the intrinsic cardiac nerves of canine hearts is characterized by enhanced release of ACh.

Acetylcholine↗
PubMed1987

Source of intrinsic innervation of canine ventricles: a functional study.

Recently it has been suggested that the parasympathetic innervation of the ventricles is by way of postganglionic axones that emanate from ganglion cells in the atria, reaching the ventricles by traversing the atrioventricular (AV) groove. We designed a series of experiments to test this hypothesis. Phenol (89%) was applied to the AV groove and surrounding 5 mm of epicardium in 21 dogs on cardiopulmonary bypass. The effects of intracoronary acetylcholine (ACh; 1-5 micrograms) and intracoronary nicotine (NIC; 25-100 micrograms) on cardiac isovolumic pressures were evaluated after beta-blockade. In another series of experiments, eight dogs were exposed to phenol in the same way and allowed to recover for 7-10 days. Atrial and ventricular responses to NIC were unaffected by phenol application to the AV groove in the acute animals when compared with application of saline alone. However, in the chronic animals, pretreatment with phenol 7-10 days previously reduced the ventricular responses to NIC by 70% while leaving the atrial responses intact. These data indicate that the intrinsic cardiac nerves (ICN) of the canine ventricles consist primarily of postganglionic parasympathetic axones which arise from supraventricular ganglia and cross the AV groove.

Acetylcholine↗
PubMed1987

Atrioventricular responses of canine heart following chronic unilateral vagotomy.

The intrinsic cardiac nerves (ICN) have been shown to develop supersensitivity to nicotine (NIC) following complete extrinsic cardiac denervation. The present experiments were performed to delineate the pattern of ICN distribution in the heart by examining the pattern of NIC supersensitivity after unilateral vagotomy (VGX). Thirty-eight dogs were placed on cardiopulmonary bypass and inotropy evaluated by means of isovolumic pressures from fluid-filled balloons placed in the atria and ventricles. The animals were divided into three groups: group I, sham-operated controls; group II, animals studied 1-2 wk after VGX; and group III, animals studied 8-12 wk after VGX. Chronotropic and inotropic responses were evaluated in terms of NIC and acetylcholine (ACh) dose-response curves as well as frequency-response curves to stimulation of the intact vagus nerve (0.5-30 Hz). No change in NIC sensitivity was observed in group II, and vagal frequency-response curves were identical to group I. In group III dogs, both the right atrium and right ventricle showed significant increases in NIC sensitivity after left vagotomy. All group III animals showed right-shifted frequency-response curves. We conclude that nicotinic supersensitivity of the ICN and inotropic unresponsiveness to vagal stimulation occur but are slow in developing (70-130 days); and preganglionic sprouting does not appear to play a functional role in the adjustment of cardiac control mechanisms to unilateral vagotomy.

Acetylcholine↗
PubMed1985

Comparison of in vivo and in vitro cholinergic responses of normal and denervated canine hearts.

Ten dogs were subjected to total extrinsic cardiac denervation. The negative inotropic responses of their hearts were compared with those of nine normal controls with respect to acetylcholine (ACh; 0.1-1.0 micrograms) and nicotine (0.5-100 micrograms) administered intra-coronary. The dogs were on cardiopulmonary bypass and atrial and ventricular contractility were measured by means of a four-chamber isovolumic technique. At the end of this phase of the experiment, atrial strips were removed for in vitro evaluation of negative inotropic responses to Ach (1 X 10(-8) to 1 X 10(-6) M) and nicotine (1 X 10(-6) to 1 X 10(-4) M). Both in vivo and in vitro methods demonstrated a leftward shift of the dose-response curve for nicotine in denervated hearts, indicative of denervation hypersensitivity. Hypersensitivity to ACh was seen in atria in vitro but not in vivo. An additional 13 dogs were used only for in vitro studies. There was no difference in response between these dogs and those which had been used for both in vivo and in vitro studies. The results support the in vivo observation that the intrinsic cardiac neurons become supersensitive to nicotinic activation after extrinsic denervation. In addition, in vitro testing revealed atrial hypersensitivity to ACh which was not detected by in vivo methods. Inasmuch as the in vivo and the in vitro testing were done on the same animals, a method for determining equivalence for in vivo doses and in vitro concentrations is presented.

Acetylcholine↗