Role of cardiac vagal C-fibers in cardiovascular control.

Digitalis glycosides exert both excitatory and inhibitory autonomic actions in animals and produce vasoconstriction in normal humans but produce vasodilation in heart failure patients. To determine whether or not these contrasting vascular responses are due to differing autonomic actions of the drug, we compared the responses to intravenous administration of Cedilanid-D (0.02 mg/kg) in eight normal subjects (mean age, 23 +/- 1 years) and eight patients with moderate-to-severe heart failure (mean age, 52 +/- 5 years, NYHA Class III-IV). Hemodynamics and efferent sympathetic nerve activity to muscle (MSNA) were measured during 5-minute periods before (control) and 20 minutes after drug administration. In the heart failure patients, Cedilanid-D significantly increased systolic and pulse pressures, whereas mean arterial pressure was unchanged. There was a decrease in right atrial pressure and a tendency for a decrease in pulmonary artery diastolic pressure with a slowing of heart rate. Cardiac index increased by 24 +/- 7%. Short-term administration of digitalis in these heart failure patients produced a fall in forearm vascular resistance (from 37.6 +/- 8.2 to 31.8 +/- 8.1 units, p less than 0.05) and an early, profound, and sustained decrease in MSNA (from 831.0 +/- 118.4 to 474.4 +/- 103.6 units/100 heart beats, p less than 0.01). Digitalis glycosides produced different vascular and MSNA responses in the normal subjects. In the normal volunteers, the drug significantly increased systolic, mean, and pulse pressures and decreased central venous pressure and heart rate. Despite the significant increase in arterial pressure, there was no change in forearm vascular resistance (from 11.7 +/- 1.0 to 12.7 +/- 1.0 units, p = NS) or MSNA (from 494.8 +/- 88.5 to 369.1 +/- 60.5 units/100 heart beats, p = NS), suggesting a sympathoexcitatory response in normal subjects. To determine whether or not the digitalis-induced sympathoinhibition in the heart failure patients was simply due to an inotropic effect (stimulation of inhibitory cardiac mechanoreceptors), we studied the responses of seven additional patients with heart failure before and during administration of dobutamine (3.4 +/- 0.4 micrograms/kg/min). Dobutamine produced a 34 +/- 3% increase in cardiac index, no significant change in systemic arterial pressures, a decrease in pulmonary artery diastolic and right atrial pressures, and no change in heart rate or forearm vascular resistance (from 30.2 +/- 4.3 to 26.5 +/- 4.7 units, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)

Sympathoinhibitory responses to digitalis glycosides in heart failure patients. Direct evidence from sympathetic neural recordings.

The sections in this article are:


1
Techniques
1.1
Carotid Sinus Massage

1.2
Electrical Stimulation of Carotid Sinus Nerves

1.3
Section or Anesthesia of Carotid Sinus Nerves and Vagi

1.4
Occlusion of Common Carotid Arteries

1.5
Neck Chamber

1.6
Vasoactive Drugs

1.7
Nonselective Techniques




2
Arterial Baroreceptor Control of Heart Rate
2.1
Autonomic Mediation

2.2
Other Properties

2.3
Relationship to Base-Line R-R Interval

2.4
Relationship to Respiratory Cycle




3
Arterial Baroreceptor Control of Atrioventricular Conduction and Ventricles

4
Carotid Baroreceptor Control of Blood Pressure

5
Carotid Baroreceptor Influence on Cardiac Output and Total Peripheral Resistance

6
Arterial Baroreceptor Control of Regional Circulations

7
Arterial Baroreceptor Control of Veins

8
Set Point of Carotid Baroreflex

9
Aortic Baroreflexes

10
Factors That Modify Arterial Baroreceptor Control of Circulation
10.1
Age

10.2
Exercise

10.3
Mental Stress

10.4
Sleep

10.5
Anesthesia

10.6
Central Blood Volume and Posture




11
Pathological States
11.1
Hypertension

11.2
Heart Disease

11.3
Carotid Sinus Syndrome

11.4
Other Pathological Conditions




12
Modification of Arterial Baroreflexes by Drugs
12.1
β-Adrenergic Antagonists

12.2
Cardiac Glycosides

12.3
Antihypertensive Drugs

Arterial Baroreflexes in Humans

THE idea that reflexes originating in the heart can play a role in normal physiology dates to the 1860s. Until the 1950s, these reflexes, and the Bezold–Jarisch reflex (BJR) in particular, were regarded largely as pharmacological curiosities with the only practical application of the study of the BJR being the clinical use of a veratrum alkaloid as an antihypertensive agent. Since the 1860s, it had been known that injection of minute amounts (0.005 mg) of veratrine or its pure alkaloid components (veratrum) initiates a reflex which causes a rapid fall in blood pressure and heart rate in association with apnea. This “Von Bezold reflex” was classically defined in association with arrest of breathing, but more recently, it has been called the BJR and includes the triad of bradycardia, hypotension, and peripheral vasodilation. It is now understood that certain inhibitory reflexes, which have origin with cardiac sensory receptors, play a role in cardiovascular homeostasis. Activation of a subset of these receptors by diverse stimuli increases parasympathetic nervous system activity, inhibits sympathetic activity and is responsible for eliciting the BJR. Some anesthesiologists have suggested that the BJR may explain cardiovascular collapse reported during regional anesthesia techniques. This review focuses on the physiology of the BJR and its possible physiologic role in a number of clinical situations. It also provides discussion of the limited relevance of this reflex in regional anesthesia. The topic of clinical management will not be addressed given the paucity of data on this matter, but suggestions for future experimental direction are offered.

Clinical relevance of the Bezold-Jarisch reflex.

Cardiac dysfunction in animals has been associated with impairment of arterial and cardiopulmonary baroreflex control of the circulation. Chronic heart failure in human beings is associated with neurohumoral excitation, which could result in part from impairment in the inhibitory influence of baroreflexes. We postulated that (1) patients with left ventricular dysfunction (LVD) have impaired baroreflex modulation of vascular resistance and (2) administration of a digitalis glycoside would immediately restore baroreflex sensitivity. Eleven patients with LVD (NYHA class, 2.8 +/- 0.2, mean +/- SEM; baseline left ventricular ejection fraction, 18 +/- 2%; cardiac index, 2.4 +/- 0.21/min/m2; and pulmonary capillary wedge pressure, 26.0 +/- 3.2 mm Hg) were compared with 17 normal control subjects. We measured forearm vasoconstrictor responses to simulated orthostatic stress with use of lower body negative pressure (LBNP) at -10 and -40 mm Hg to unload cardiopulmonary and arterial baroreceptors. Baseline forearm vascular resistance (FVR) was higher in patients with LVD than in normal subjects: FVRLVD, 68.8 +/- 15.3 U; FVRN, 23.2 +/- 2.1 U (p less than .001). During unloading of baroreceptors with LBNP -10 mm Hg, normal subjects developed vasoconstriction (delta VRN at LBNP -10 mm Hg, +5.7 +/- 1.6 U) but patients with LVD failed to have vasoconstriction and tended to develop vasodilation (delta FVRLVD at LBNP -10 mm Hg, -8.6 +/- 8.5 U) (p = .05, normals vs patients with LVD at LBNP -10 mm Hg). A more marked disparity in response was seen during unloading of baroreceptors of LBNP -40 mm Hg: delta FVRN at LBNP -40 mm Hg, +16.6 +/- 1.5 U; delta FVRLVD at LBNP -40 mm Hg, -10.3 +/- 9.6 U (p less than .001, normals vs patients with LVD). Despite high baseline values for FVR, patients with LVD developed vasoconstriction during intra-arterial infusions of norepinephrine, thereby excluding a nonspecific depression of vascular reactivity as the mechanism for abnormal responses to LBNP in patients with LVD. We also studied the short-term effects of administration of a digitalis glycoside, ouabain 0.0075 mg/kg (seven patients) or lanatoside C (Cedilanid-D) 0.02 mg/kg (three patients), on baroreflex-mediated vasoconstrictor responses to LBNP in the patients with LVD. Digitalis glycoside reduced baseline FVR from 71.8 +/- 16.6 to 48.6 +/- 12.0 U (p less than .02). Responses to LBNP tended to be normalized after administration of digitalis glycoside: delta FVR during LBNP -40 mm Hg, -11.1 +/- 10.5 U before and +7.8 +/- 5.6 U after the drug (p less than .05).(ABSTRACT TRUNCATED AT 400 WORDS)

Selective impairment of baroreflex-mediated vasoconstrictor responses in patients with ventricular dysfunction.

Activity from left ventricular receptors with non-medullated afferents was recorded in the right cervical vagus in anesthetized, thoracotomized cats. Probing of the open heart demonstrated that the receptors were distributed throughout the free wall and the interventricular septum. Fibers from posterior receptors pass along the posterior descending coronary artery and the lateral surface of the right atrium to join the right main cardiac nerve; those from the anteriolateral region pass behind the aorta and the pulmonary trunk. The control receptor discharge was 1.4 (range, 0-6) impulses/sec at a mean left ventricular end-diastolic pressure (LVEDP) of 4.5 (range, 2-10) mm Hg. It was observed that receptor discharge increased with progressive increase in LVEDP produced either by transfusion or by aortic occlusion. At a mean LVEDP of 8 mm Hg, the mean discharge rate was 3.2 impulses/sec, and at 16 mm Hg it was 7.0 impulses/sec. It was also found that propranolol reduced and isoproterenol increased the discharge frequency at any given LVEDP. Measurement of total conduction times indicated that during the increase in LVEDP the receptors were activated principally in the systolic portion of the cardiac cycle. Despite this there was no obvious relationship between the discharge frequency and left ventricular systolic pressure.

P N Thorén

Papers

Characteristics of left ventricular receptors with nonmedullated vagal afferents in cats.