A B S T R A C T The time relationship for recovery of mechanical function, the intramyocardial electrogram and coronary flow after brief periods of regional myocardial ischemia, was studied in conscious dogs. Total left ventricular (LV) function was assessed with measurements of LV systolic and diastolic pressures, rate of change of LV pressure (dP/dt), and dP/dt/P. Regional LV function was assessed with measurements of regional segment length and velocity of shortening. An implanted hydraulic occluder on either the left anterior descending or circumflex coronary artery was inflated for 5-and 15-min periods on separate days. A 5-min occlusion depressed overall LV function transiently, but just before release of occlusion overall function had nearlv returned to control. At this time regional function in the ischemic zone was still depressed to the point of absent shortening or paradoxical motion during systole and was associated with marked ST segment elevation (+ 10± 2.2 mV) at the sites where function was measured. With release of occlusion and reperfusion the intramyocardial electrogram returned to normal within 1 min, and reactive hyperemia subsided by 5-10 min. In contrast to the rapid return to preocclusion levels for coronary flow and the electrogram, regional mechanical function remained depressed for over 3 h. A 15-min coronary occlusion resulted in an even more prolonged (> 6 h)

The effects of dobutamine ([±] ¶4-[2- [[3-(p-hydroxyphenyl itg/kg/min, the drug increased dP/dt/P from 65±3 to 128i4 s' and isolength velocity from 72±4 to 120+7 mm/s without affecting LV end diastolic D significantly. Mean arterial P rose from 92±2 to 104±3 mm Hg and heart rate from 78±3 to 111+7 beats/min, while LV end systolic D fell from 24.1±+1.4 to 19.9±1.8 mm, reflecting a rise in stroke volume from 30±4 to 42±3 ml. Cardiac output rose from 2.41±0.23 to 4.35±0.28 liter/min, while calculated total peripheral resistance declined from 0.042+0.005 to 0.028±0.003 mm Hg/ml/min. The greatest increases in flow and decreases in calculated resistance occurred in the iliac and coronary beds, and the least occurred in the renal bed. Propranolol blocked the inotropic and betas dilator responses while vasoconstricting effects mediated by alpha adrenergic stimulation remained in each of the beds studied. When dobutamine was infused after a combination of practolol and phentolamine, dilatation occurred in each of the beds studied. These observations indicate that dobutamine is iDr.

The Bainbridge reflex, i.e., the effect of rapid saline infusion (1.1 ± 0.1 liters) on heart rate and arterial and atrial blood pressures, was examined in 12 intact conscious dogs; mean arterial blood pressure rose by 33 ± 3 (SE) mm Hg, mean atrial pressure by 14 ± 1 mm Hg, and heart rate by 75 ± 9 beats/min. After beta-receptor blockade, heart rate rose slightly less (+49 =t 5 beats/min, P = 0.05). Cholinergic blockade, combined cholinergic and beta-receptor, or beta-receptor blockade after vagotomy blocked the heart rate response to the infusion. The rise in heart rate in the face of an increase in arterial blood pressure with volume loading suggested that the arterial baroreceptor reflex was not responding appropriately to the increase in arterial blood pressure. In conscious dogs after denervation of the arterial baroreceptors, the increase in heart rate with volume loading was no greater than that in those dogs with their arterial baroreceptors intact, suggesting that the baroreceptor reflex was not restraining heart rate in the normal response to volume loading. The relationship between the pulse interval (PI) and the systolic arterial blood pressure (SAP) following an intravenous injection of methoxamine was used to evaluate the sensitivity of the baroreceptor reflex in intact conscious dogs. After a mild amount of volume loading, when atrial pressure was 8 ± 2 mm Hg, the PI/SAP slope was significantly depressed from normal. When atrial pressure was elevated further to 28 ± 1 mm Hg by volume loading, the slope was further depressed. Thus, arterial baroreflex sensitivity is reduced progressively as atrial pressure is raised by volume loading, an observation that explains how heart rate can rise strikingly in the face of an elevated arterial blood pressure.• In 1915, Bainbridge (1) observed that a rapid infusion of saline or blood induces tachycardia, which is abolished by vagotomy; this response has been referred to as the Bainbridge reflex. The Bainbridge reflex is one of several physiological situations that does not follow Marey's law (2), which describes the inverse relationship between cardiac rate and arterial blood pressure, since volume loading results in an increase in both arterial blood pressure and cardiac rate. The infusion-induced elevation of arterial blood pressure would be expected to stimulate the arterial baroreceptors to reduce heart rate reflexly, unless a change in the gain of the reflex, the set point of the reflex, or both occurs (3). The goal of the present study was to evaluate the effects of acute volume 236loading on heart rate in the conscious dog and to examine the extent to which volume loading alters the properties of the arterial baroreceptor system.Since one of the controversies concerning the Bainbridge reflex involves the questions of whether heart rate consistently rises with volume loading and to what extent the response is related to the initial heart rate prior to volume loading (4-6), the present study was conducted in conscious dogs in which resting heart ...

A B S T R A C T The effects of isoproterenol, norepinephrine, dobutamine, exercise, and nitroglycerin on left ventricular diameter, pressure, velocity of shortening, dP/dt, dP/dt/P, arterial pressure, left circumflex coronary blood flow, and coronary vascular resistance were examined in healthy conscious dogs with normal coronary perfusion and in the same animals after moderate global ischemia had been induced by partial occlusion of the left main coronary artery. In the normal nonischemic heart, all interventions improved left ventricular performance, as evidenced by increases in dP/ dt/P and velocity at the same or lower left ventricular end-diastolic diameter. Interventions, which in the normal heart caused large increases in heart rate and myocardial contractility, e.g. isoproterenol and exercise, or which decreased coronary perfusion pressure, e.g. nitroglycerin or isoproterenol, elicited paradoxical responses in moderate global ischemia, i.e., left ventricular enddiastolic diameter and pressure rose, and dP/dt/P and velocity fell substantially. On the other hand, norepinephrine, which increased coronary perfusion pressure along with myocardial contractility but did not increase heart rate, improved left ventricular function. Dobutamine, which did not alter heart rate or arterial pressure substantially while improving myocardial contractility, produced an intermediate response between that of norepinephrine and isoproterenol in the presence of moderate

The interaction of chemoreflex and pulmonary inflation reflex control of the coronary circulation was examined in conscious dogs by comparing the responses to chemoreflex stimulation (intracarotid injection of nicotine) when ventilation was allowed to increase with those when ventilation was controlled. The responses were also compared with those elicited by both forced mechanical and spontaneous hyperinflation. When the heart rate was constant, intracarotidly administered nicotine induced an increase in the depth of respiration followed closely by an increase in late diastolic coronary flow from 48 +/- 2 to 106 +/- 8 ml/min and a reduction in late diastolic coronary resistance from 1.62 +/- 0.08 to 0.78 +/- 0.06 mm Hg/ml min-1. After beta-receptor and cholinergic blockade, a similar coronary dilation in response to nicotine occurred only when ventilation was allowed to increase. However, when ventilation was controlled, intracarotidly administered nicotine increased coronary resistance after combined beta-receptor and cholinergic blockade. The reflex coronary dilation was not observed after carotid sinus nerve section or after alpha-receptor blockade. Thus, nicotine stimulation of the carotid chemoreflex results in a striking coronary dilation that has two components. The minor component involves a chemoreflex with its efferent pathway in tthe vagi. The major component of coronary dilation follows an increase in the depth of respiration, and its efferent component appears to involve withdrawal of alpha-adrenergic constrictor tone. An almost identical period of reflex coronary dilation followed either forced mechanical or spontaneous hyperinflation in the conscious dog.

The circulatory effects of blocking cardiac and peripheral autonomic effectors were studied in 32 subjects with established essential hypertension, and in 15 normotensives. The mean resting arterial pressure, heart rate and total peripheral resistance index (TPRI) were significantly higher in the hypertensives, but cardiac index was the same in both groups. In subjects with blocked cardiac effectors (atropine + beta-blocking drugs, i.v.) the sympathetic constrictor effects on TPRI were estimated from the changes after giving i.v. guanethidine + phentolamine. The autonomic component of TPRI was higher in hypertensives than in normotensives. The residual resistance after `total' autonomic block (non-autonomic TPRI) was higher in hypertensives, accounting for 60 to 80% of the initial difference in resting TPRI between the two groups. With an increase in non-autonomic TPRI, the increased autonomic TPRI effect in hypertension is not necessarily due to increased sympathetic nerve activity. Vagal and cardiac sympathetic effects on heart rate were compared in the two groups. Each estimate was based on the average of the responses to the appropriate blocking drug (1) in subjects not previously given a blocking drug, and (2) in subjects with the other cardiac effector pathway already blocked. The higher heart rate in established hypertension was predominantly due to change in vagal rather than cardiac sympathetic effects.

Summary. Nasopharyngeal stimulation hy cigarette smoke in iinanaesthetised rabbits evokes apnoea in expiration, liradycardia (to 30% of control), a rise in mean arterial (to 110?) and right atrial pressure (by 6 mm Hg) and a fall in cardiac output (to 415^ of control) and systemic conductance (to 36%). Blood flow (measured by Doppler fiownieter) and conductance in the me.senteric. renal, hind limb and ear beds falls tmiformly between beds and to the extent that, on occasions, flow in all these beds ceases. Sagittal sinus flow and conductance, in contrast, do not change or rise. The cardiovascular response is mediated predominantly through cardiac vagal and peripheral ,';ympathetic vasoconstrictor nervous pathways. PvO^ in animals with intact autonomic reflex mechanisms falls by 10 ± 0-4 mm Ilg 25 sec after the onset of apnoea, but in animals with either combined or selective blockade of vaga! and sympathoadrenal pathways peripheral flow is not reduced as in animals with intact autonnmic pathways, and PvOg falls by a significantly greater but equal amount in each (av. 15 ± 0-6 mm Hg, p,,j,f < 0-001). The circulatory changes thus appear to conserve body oxygen stores during the induced apnoea, an effect dependent on the integration of evoked vagal an

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