Yoshito Nagashima

PACAP-38 activates parasympathetic nerves in isolated, blood-perfused dog atria

A pituitary adenylate cyclase-activating polypeptide (PACAP) activates PACAP and vasoactive intestinal peptide (VIP) receptors. We investigated the effects of PACAP-38 on the sinus rate and atrial contractile force in isolated, blood-perfused dog heart preparations and the stimulation by PACAP-38 of the parasympathetic nerve fibers. PACAP-38 (3-1000 pmol) caused positive and/or negative chronotropic responses and it dose dependently increased atrial and ventricular contractile force. The positive cardiac responses to PACAP-38 unlike those to VIP were much less than the positive responses to norepinephrine. Atropine inhibited the negative chronotropic responses to PACAP-38 and augmented the positive chronotropic and inotropic responses. Physostigmine potentiated the negative cardiac responses to PACAP-38 and acetylcholine. After physostigmine treatment, additionally, tetrodotoxin blocked the negative cardiac responses to PACAP-38 and intracardiac parasympathetic nerve stimulation. Propranolol did not inhibit the positive cardiac responses to PACAP-38 in atropine-treated atria. PACAP-(6-38) (1 and 3 nmol), an antagonist of PACAP-38, did not affect the cardiac responses to 100 pmol of PACAP-38. These results suggest that (1) PACAP-38 directly increases sinus rate and atrial contractile force and (2) PACAP-38 activates parasympathetic nerves and causes negative chronotropic and inotropic responses in the dog heart.

Effects of PACAP-38 on the SA nodal pacemaker activity in autonomically decentralized hearts of anesthetized dogs.

Pituitary adenylate cyclase-activating polypeptide (PACAP) receptors exist, but the physiologic role of PACAP is unclear in the heart in situ. We investigated effects of PACAP-38 on sinus rate and on the negative chronotropic response to acetylcholine (ACh) or stimulation of the intracardiac parasympathetic nerve fibers to the sinoatrial nodal region in the automatically decentralized heart of the open chest, anesthetized dog. PACAP-38 (0.1-1 nmol) injected directly into the sinus node artery caused transient positive followed by negative chronotropic responses. Both pretreatment with atropine and tetrodotoxin inhibited the negative chronotropic responses to PACAP-38. However, hexamethonium did not block the negative responses to PACAP-38. After treatment with PACAP-38 (0.1-1 nmol), ACh induced atrial fibrillation significantly (p < 0.01). On the other hand, the negative chronotropic responses to intracardiac parasympathetic stimulation were not changed. These results suggest that (a) PACAP-38 induces negative chronotropic responses and liberates ACh from intracardiac postganglionic parasympathetic nerves, and that (b) PACAP-38 reduces ACh-induced atrial fibrillation threshold in the dog heart in situ.

PACAP-27 causes negative and positive dromotropic effects in anesthetized dogs

While pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified radioimmunologically in the rat heart, the physiological role of PACAP has not been elucidated in the regulation of the atrioventricular conduction in the heart. We, therefore, determined the dromotropic effects of PACAP-27 injected into the cannulated atrioventricular node artery in the autonomically decentralized heart of the open-chest, anesthetized dog. PACAP-27 caused transient positive followed by negative dromotropic responses in a dose-dependent manner, whereas vasoactive intestinal peptide (VIP) caused only a positive dromotropic response. Atropine and tetrodotoxin blocked the negative dromotropic response to PACAP-27 and after blockade PACAP-27 caused only a positive dromotropic response. Tetrodotoxin and propranolol did not affect the positive dromotropic response to PACAP-27 in atropine-treated dogs. PACAP-27 altered the atrio-His bundle interval but did not alter the His-ventricle interval. These results demonstrate that PACAP-27 prolongs the atrio-His bundle interval due to the liberation of acetylcholine from parasympathetic nerves and decreases it by a non-adrenergic mechanism in the dog heart in situ.

Cardiac effects of propofol and its interaction with autonomic nervous system in isolated, cross-circulated canine atria

AbstractPurpose. The effects of propofol on sinoatrial pacemaker activity and myocardial contractility and its interaction with the autonomic nervous system were investigated in isolated, cross-circulated right atrial canine preparations. Methods. An isolated right atrial preparation was perfused with heparinized arterial blood from an anesthetized support dog and changes in atrial rate and atrial contractile force were recorded. Results. Propofol (30–1000 μg) and thiopental (30–1000 μg), injected into the sinus node artery of the isolated atrium, induced dose-dependent decreases in atrial rate and contractile force. The negative chronotropic and inotropic effects of propofol were greater than those of thiopental. The propofol-induced negative chronotropic and inotropic responses were not inhibited by atropine. Propofol had no effects on the cardiac responses to acetylcholine, norepinephrine, and the intracardiac parasympathetic nerve stimulation which activates ganglionic nicotinic acetylcholine receptors. Conclusion. These results indicate that: (a) propofol directly depresses sinoatrial pacemaker activity and myocardial contractility, (b) the negative chronotropic and inotropic effects of propofol do not involve activation of muscarinic receptors, and (c) propofol has little interaction with the autonomic nervous system at the effector site.

Propofol decreases contractility of isolated blood-perfused left ventricular muscle in the dog

heparin was administered. The left ventricular muscle along the anterior descending branch of the left coronary artery was then excised and immersed in cold Ringer’s solution at about 4°C. The wet weight of the isolated left ventricular preparations varied from 8 to 15 g. The anterior descending branch was cannulated and perfused with heparinized blood conducted from the common carotid artery of the support dog with the aid of a peristaltic pump (model 1210; Harvard Apparatus). A pneumatic resistance was placed in parallel with the perfusion system so that a constant perfusion pressure of 100 mmHg could be maintained. The venous effluent from the preparation was led to a blood reservoir and returned to the support dog through the external jugular vein. The isolated ventricular muscle was driven by an electrical stimulator (SEN 7103; Nihon Kohden, Tokyo, Japan) with a pulse duration of 1 ms and 4 V pulse amplitude at a frequency of 2Hz. The superior part of the ventricle was connected to a forcedisplacement transducer (AP620G; Nihon Kohden) by a silk thread to measure the isometric tension. The muscle was loaded with a resting tension of 2g. In the first series of experiments, we investigated the changes in heart rate and arterial blood pressure of the support dog and the concomitant changes in contractile force of the isolated left ventricle (n 5 5) when propofol (0.3–3 mg·kg21) was administered to the external jugular vein of the support dog. Each dose of propofol was given cumulatively at 10-min intervals. In the second series, to compare the negative inotropic effects of propofol and thiopental, both drugs (30–1000 μg) were injected into the anterior descending branch of the left coronary artery of the isolated ventricle (n 5 6). The results are shown as maximal percentage changes from predrug values and are expressed as mean 6 SEM. The data were analyzed by an analysis of variance and Bonferroni’s method for multiple comparisons of data. P values less than 0.05 were considered statistically significant.

Chronotropic and inotropic effects of terikalant on isolated, blood‐perfused atrial and ventricular preparations of dogs

Summary— We investigated the effects of terikalant, which blocks inward rectifier K+ current, on the sinus rate, atrial and ventricular contractile force in the isolated, blood‐perfused right atrial and left ventricular preparations of dogs, and the effects of terikalant on the negative cardiac responses to acetylcholine, adenosine or pinacidil (an ATP‐sensitive K+ channel opener) and on the positive cardiac responses to norepinephrine. Terikalant (1–100 nmol) decreased sinus rate and briefly and slightly increased atrial contractile force in isolated atria. However, terikalant did not increase ventricular contractile force in isolated ventricles. Neither propranolol nor atropine inhibited the positive inotropic and negative chronotropic responses to terikalant, respectively. Terikalant (10 or 30 nmol) did not significantly affect the negative cardiac responses to acetylcholine, adenosine nor pinacidil and the positive responses to norepinephrine. These results suggest that terikalant decreases sinus rate with a small changes in myocardial contractile force and does not affect the cardiac responses to muscarinic and adenosine receptor agonists, ATP‐sensitive K+ channel openers nor β‐adrenoceptor agonists in the dog heart.

Anesthesia for laparoscopic cholecystectomy in an elderly patient with emphysematous bullae : combined general and epidural anesthesia with spontaneous respiration and abdominal wall-left method

Laparoscopic cholecystectomy is rapidly gaining popularity with surgeons and patients, but as the popularity of this technique increases and the selection of patients widens to older and sicker people, careful considerations in anesthetic management are required. We recently experienced a case of laparoscopic cholecystectomy with emphysematous bullae. To avoid the risk of barotrauma, we adopted an abdominal wall-lift method without peritoneal insufflation, and maintained anesthesia with spontaneous respiration.