Phylogenesis of the Bainbridge reflex.

The effects of volume loading were examined on measurements of left ventricular (LV) pressure and heart rate in patients undergoing cardiac catheterization. These data were compared to those collected in conscious dogs and subhuman primates (baboons). In man acute volume loading increased LV end-diastolic pressure by 14 mmHg, but did not increase LV systolic pressure significantly. Similar increases in LV end-diastolic pressure were observed in conscious dogs and baboons. LV systolic pressure also did not rise in baboons, but did increase (+32 mmHg) with volume loading in dogs. In man volume loading increased heart rate by 15 beats/min, significantly less (P less than 0.01) than observed in baboons (+37 beats/min), and which in turn was significantly less than that observed in dogs (+88 beats/min). Thus, the Bainbridge reflex, i.e., the tachycardia that occurs with volume loading, appears to exist in primates including man. However, the extent of utilization of this reflex decreases significantly from nonprimate mammals (dogs) to subhuman primates (baboons) to man.

Extent of utilization of the Frank-Starling mechanism in conscious dogs.

The extent to which an increase in preload increases left ventricular (LV) end-diastolic (ED) diameter (D) was studied in seven conscious dogs instrumented with ultrasonic D transducers and miniature LV pressure (P) gauges. Preload was elevated by three techniques: 1) volume loading with saline infusion, 2) induction of global myocardial ischemia by constricting the left main coronary artery, and 3) infusion of methoxamine. These three interventions increased LVEDP to over 30 mmHg from a control of 10 +/- 1 mmHg. With volume loading, LVEDD rose by only 1.55 +/- 0.39 mm from a control of 44.08 +/- 1.08 mm; with ischemia LVEDD rose by only .96 +/- .29 mm from a control of 42.55 +/- 2.18 mm, while with methoxamine LVEDD rose by only 1.34 +/- 0.38 mm from a control of 43.89 +/- 2.07 mm. In contrast, in the open-chest, anesthetized dog, LVEDD was greatly reduced and volume expansion resulted in a profound increase in LVEDD. Thus, the Frank-Starling mechanism is not an important controlling mechanism in the normal, reclining, conscious animal, since LVEDD appears to be near maximal at rest and does not increase substantially despite striking increases in LVEDP.

Effects of angiotensin, vasopressin, and methoxamine on cardiac function and blood flow distribution in conscious dogs.

A comparison was made of the effects of vasopressin (ADH), methoxamine (MX), and angiotensin II (AN) on coronary and left ventricular dynamics, cardiac output, and regional blood flow distribution in intact, consci9us dogs. At an equal percent pressure elevation, ADH reduced cardiac output and cardiac rate the most, while AN had the least effect. After denervation of arterial baroreceptors, ADH still reduced heart rate, while AN increased it, suggesting nonbaroreceptor negative and positive chronotropic effects, respectively. A differential pattern on peak dP/dt was also observed, with ACH causing a greater reduction than MX while AN did not decrease dP/dt. With heart rate held constant, AN did not reduce dP/dt, suggesting a direct positive inotropic effect since dP/dt should have fallen slightly due to reflex mechanisms, as was observed with MX and ADH. ADH induced the greatest increase in coronary resistance (140%), while the least (46%) was observed with AN, which could be explained, in part, by the differential effects observed on cardiac rate and contractility. The greatest increase in resistance in the iliac bed occurred with ADH (30%), and the least with AN (34%). Conversely, the greatest constriction in the renal bed occurred with AN (95%), and lesser amounts were observed with ADH (36%) and MX (35%). Thus ADH, MX, and AN exert potent yet differential vasoconstricting actions on peripheral beds. In addition, while all three agents elicited coronary vasoconstriction, the differential effects on coronary vascular resistance appeared to be due predominantly to a difference in chronotropic and inotropic actions.

Prostaglandin control of renal circulation in the unanesthetized dog and baboon.

Effects of indomethacin and meclofenamate, inhibitors of prostaglandin synthesis, were evaluated in the regulation of renal blood flow in conscious and anesthetized dogs and in tranquilized baboons, instrumented with arterial pressure catheters and renal blood flow probes. Indomethacin, 10 mg/kg, did not alter renal blood flow or resistance significantly in the conscious dog. In the anesthetized dog, however, indomethacin caused a reduction in renal blood flow (25 +/- 3% of control) and an elevation of renal vascular resistance (45 +/- 8% of control). Meclofenamate, 4 mg/kg, reduced renal flow (12 +/- 2%) and increased renal vascular resistance 15 +/- 4% in conscious dogs. In conscious dogs and tranquilized primates, indomethacin and meclofenamate reduced the reactive hyperemia in the renal bed after 15 s occlusion from a control of 36 +/- 5 ml to 6 +/- 2 ml, and after 45 s occlusion from a control of 98 +/- 9 ml to 17 +/- 5 ml. Methoxamine (10-50 mug/kg per min) and angiotensin II (0.03-0.12 mug/kg per min), infused in graded doses, induced significantly greater renal vasoconstriction in conscious dogs in the presence of indomethacin. Thus, in the conscious animal, prostaglandins appear to play only a minor role in the control of the renal circulation at rest, but are of greater importance in mediating the renal responses to reactive hyperemia and to vasoconstriction.

Reduced baroreflex sensitivity with volume loading in conscious dogs.

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 +/- 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.