Effects of vasoactive intestinal polypeptide on heart rate in relation to vagal cardioacceleration in conscious dogs.

OBJECTIVE: The vagal cardiac accelerator (VCA) system takes part in the nervous control of the heart rate. In the present study we tried to adduce evidence that vasoactive intestinal polypeptide (VIP) contributes to vagally induced cardioaccelerations. METHODS: The effect of VIP on heart rate and arterial blood pressure was investigated after unmasking the inherent VCA activity by blocking the sympathetic accelerator and vagal decelerator influences on heart rate in conscious dogs. RESULTS: Following intravenous administration of VIP (10 micrograms i.v.) the heart rate increased by 43.6 +/- 6.7 (28.1 +/- 4.7%), from 165.6 +/- 8.5 to 209.1 +/- 7.0 beats/min (P < 0.001) and the mean arterial blood pressure decreased by 47.5 +/- 3.2 (37.9 +/- 3.0%), from 126.6 +/- 2.6 to 79.1 +/- 4.9 mmHg (P < 0.001) (n = 11). After VCA activity was reflexly enhanced by alpha 1-adrenoceptor stimulation with methoxamine, VIP increased heart rate by 36.9 +/- 7.3 (21.5 +/- 4.6%), from 179.8 +/- 5.2 to 216.7 +/- 5.8 beats/min (P < 0.001) and decreased mean arterial pressure by 79.1 +/- 6.4 (46.7 +/- 3.5%), from 168.2 +/- 4.1 to 89.1 +/- 5.0 mmHg (P < 0.001). Hence, the VIP-induced tachycardia, expressed in relative values, shows a significant attenuation after the administration of methoxamine (P < 0.05). The increase in heart rate induced by VIP appeared to be inversely related to the prevailing VCA activity, both before (r = -0.744, P = 0.009) and after methoxamine (r = -0.689, P = 0.019). The VIP-induced tachycardia is certainly not reflexly induced by the fall in arterial pressure, because intracoronary administration of VIP (0.5 microgram i.c.) caused an appreciable increase in the heart rate by 63.7 +/- 13.0 (46.4 +/- 10.4%), from 143.0 +/- 8.1 to 208.7 +/- 12.0 beats/min (P < 0.005), whereas the mean arterial pressure only slightly changed (-7.7 +/- 2.0 mmHg) (P < 0.05) (n = 6). In addition, VIP (10 micrograms i.v.) also caused a tachycardia in vagotomized dogs with blocked beta-adrenergic and muscarinic receptors. The administration of the VIP antagonists [D-p-CI-Phe6, Leu17]-VIP (50-150 micrograms i.c.) and [Lys1, Pro2,5, Leu17]-VIP (20 micrograms i.c.) did not result in alterations in VCA activity nor did the VIP antagonists block the VCA reflex response to a rise in arterial pressure. However, none of the VIP antagonists reduced the VIP-induced tachycardia either. CONCLUSION: Vasoactive intestinal polypeptide is likely to play a part in the vagal cardiac accelerator system. However, conclusive evidence for its role as the terminal transmitter in the VCA pathway will have to wait for the availability of a specific cardiac VIP receptor antagonist.

Cardioacceleratory effect of muscarinic blocking agents in the dog.

To test whether the tachycardia in response to atropine after adrenergic blockade is partly due to a central excitatory action, the effects of atropine, methylatropine and methylscopolamine were compared in dogs in neurolept-anesthesia. The latter two agents proved to have effect, similar to atropine. A central action is therefore improbable. It was possible to partly abolish the tachycardia by hexamethonium. The cardioacceleration by atropine, methylatropine and methylscopolamine, so far as it is not caused by muscarinic receptor blockade, can be explained by the unmasking of an underlying acceleratory tone.

Weight loss in full-term negroid infants: relationship to body water compartments at birth?

The possible influence of the body fluid compartments at birth on postnatal weight loss was studied in normal term negroid infants when on a standardized oral fluid, sodium and energy regimen during the first three days of life. Measurements of plasma volume (PV), total body water (TBW), and extracellular water (ECW) were performed simultaneously on vaginally-born infants on the first day of life, by using a triple indicator (Evans blue, deuterium oxide and sucrose) single injection dilution technique. PV was 54 +/- 7 ml/kg (N = 9), TBW was 751 +/- 50 ml/kg (N = 13) and ECW was 311 +/- 61 ml/kg (N = 13) (mean +/- S.D.). Postnatal weight loss (3.7% of birth weight) occurred during the first two days. The postnatal weight loss was not related to any of the body water compartments. However, there was a highly significant correlation with the (cumulative) urine water excretion (r = 0.833, P less than 0.001 on day 1, with similar values for days 1 and 2).

Simultaneous perfusion of both coronary arteries and drainage of the coronary sinus in the dog heart in situ.

A technique is described for perfusion of the entire coronary arterial system of the dog heart in situ and for drainage of the coronary sinus blood. Both coronary arteries are cannulated without ligation of major ventricular branches and disconnected from the aorta. The cannulas are connected to an extracorporeal system allowing perfusion under controlled pressure, without ill effects to either the heart or the blood. The arterial perfusion system is fed from the femoral arteries of the dog. The coronary sinus is cannulated for draining the blood to a venous reservoir against a controlled pressure. From the reservoir the blood is pumped into a femoral vein. Thus a preparation is obtained in which the interdependency of coronary circulation and performance of the heart has been discontinued. Under careful monitoring of pressures and flows, and of blood temperature, blood gases and plasma electrolytes, the preparation has been kept in excellent condition for up to 7 hrs.

Intrinsic heart rate in the dog determined by pharmacologic denervation.

Intrinsic heart rate was measured in 19 dogs in 76 experiments after autonomic blockade, using various forms of anesthesia. Measurements were made in conscious dogs (n = 16) and in dogs in neuroleptanesthesia (n = 54) or under pentobarbital sodium (n = 6). Temperature, arterial pH, and blood gases were kept within narrow limits. Adrenergic blockade was achieved by phenoxybenzamine (2 mg X kg-1) and propranolol (2 mg X kg-1, followed by 2 mg X kg-1 X h-1). The parasympathetic system was blocked either by atropine (0.5 mg X kg-1, followed by 0.5 mg X kg-1 X h-1) and hexamethonium (20 mg X kg-1, followed by 10 mg X kg-1 X h-1) or by atropine and bilateral cervical vagotomy. Administration of hexamethonium or vagotomy was needed to block the vagal cardioacceleration unmasked by the administration of muscarinic blocking agents in conscious dogs and in dogs in neuroleptanesthesia. The mean denervated heart rate was 142.8 beats/min. This value is higher than that reported for surgically denervated hearts, the difference very likely reflecting the activity of the intact parasympathetic intrinsic cardiac innervation in surgical preparations. The estimated intraindividual and interindividual SD were 9.7 and 19.4 beats/min, respectively. The highly significant interindividual variation (P less than 0.01) contradicts the concept of an intrinsic heart rate as a practically constant species-dependent quantity.

Mechanism of the decline in vagal cardiac acceleration in dogs in neuroleptanaesthesia.

Muscarinic receptor blockade in beta-adrenoceptor blocked dogs in neuroleptanaesthesia reveals a vagally-mediated cardiac acceleration ('inherent VCA'); the heart rate reaches a maximum level within 10 min, then declines spontaneously. Experiments were designed to settle whether the decline in the VCA is due to a decrease in peripheral responsiveness and/or a decrease in central vagal tone. The decline in VCA was assessed in one group of dogs (n = 12) over a period of 170 min, after which ganglionic nicotinic blockade (Exp 1) or vagotomy (Exp 2) was carried out. The maximum 'inherent VCA', defined as the difference between maximum heart rate after muscarinic blockade and the rate after nicotinic blockade or vagotomy, was 68 +/- 10 and 64 +/- 11 bpm, respectively. The VCA declined to 75, 50 and 25% of the maximum levels after 23 +/- 7, 42 +/- 8 and 127 +/- 18 min (Exp 1) or 21 +/- 4, 51 +/- 12 and 113 +/- 20 min (Exp 2). The maximum heart rate in response to electrical vagal stimulation (maximum 'stimulation VCA') was established according to two scenarios in two groups of dogs matched for maximum 'inherent VCA' (n = 7). In the 0-min (Exp 3) and 170-min scenario (Exp 4) vagotomy was carried out 10 and 180 min after the muscarinic blockade. Expressed as percentage of the maximum 'inherent VCA', the maximum 'stimulation VCA' was 116 +/- 7 and 41 +/- 8%, respectively. This implies that the peripheral neuroeffector responsiveness declined by 75% over the given time period.(ABSTRACT TRUNCATED AT 250 WORDS)

The vagal cardiac accelerator system in the reflex control of heart rate in conscious dogs.

The reactions of the vagal cardioaccelerator (VCA) system to changes in mean arterial pressure (MAP) were studied in five beta-adrenoceptor blocked conscious dogs. An increase in MAP was obtained by administration of vasopressin or methoxamine, a decrease by doxazosin or nitroprusside. In the first series of experiments the MAP changes were induced after muscarinic receptor blockade, in a second series both before and after muscarinic blockade. Prior to these experiments, the maximum VCA activity, defined as the difference between maximum heart rate after muscarinic blockade and the rate after additional nicotinic blockade, was determined. We hypothesized that this quantity, as a measure of VCA activity, depends on the prevailing vagal tone. In the first series of experiments, a rise in MAP evoked an increase in heart rate, a fall in MAP indicated decrease. In the second series, when prior to muscarinic blockade the vagal tone was reflexly raised, the subsequent VCA reflex response to the rise in MAP was attenuated. Prior to the muscarinic blockade the vagal tone was reflexly lowered, the VCA reflex response was enhanced. Direct chronotropic effects of MAP-varying drugs were ruled out by the absence of a heart-rate response in experiments on vagotomized animals. We concluded that the vagal cardioaccelerator system is involved in the reflex control of heart rate. Both the VCA reflex response to changes in systemic blood pressure and the maximum VCA activity however, are determined by the prevailing vagal tone.

Outflow from the left and the right coronary artery into the coronary sinus in the dog heart in situ.

The fractions of the left and the right coronary arterial flow determining coronary sinus flow (facs, facd) were measured in the open-chest dog. Both coronary arteries were isolated and perfused at the same pressure, while the sinus outflow was isolated and drained against the prevailing mean pressure in the right atrium. The fractions were determined by injecting 51Cr labeled erythrocytes into each coronary artery selectively and measuring the total resulting radioactivity in the sinus blood. In addition, they were estimated from flow measurements. The values of facs and facd were found to approximate 0.70 and 0.02 respectively. The variability between the different dog hearts was considerable and it was demonstrated that they were not intercomparable with respect to their coronary flow distribution.

Incomplete cardiac vagal blockade with atropine in the anesthetized dog.

In dogs in neurolept-anesthesia the successive administration of alpha- and beta-adrenergic blocking agents and atropine, which should cause the functional equivalent of surgical denervation of the heart, always results in a marked tachycardia. The same is observed in conscious dogs, but not during methoxyflurane anesthesia. Bilateral vagotomy and administration of hexamethonium abolish the tachycardia. These observations demonstrate the presence of a vagally mediated chronotropic effect which becomes manifest when the inhibitory vagal effect is eliminated through blockade of the muscarinic receptors with atropine.