The sequence of neural responses to exogenous arterial pressure manipulation remains unclear, especially for extramedullary sites. We used functional magnetic resonance imaging procedures to visualize neural responses during pressor (phenylephrine) and depressor (sodium nitroprusside) challenges in seven isoflurane-anesthetized adult cats. Depressor challenges produced signal-intensity declines in multiple cardiovascular-related sites in the medulla, including the nucleus tractus solitarius, and caudal and rostral ventrolateral medulla. Signal decreases also emerged in the cerebellar vermis, inferior olive, dorsolateral pons, and right insula. Rostral sites, such as the amygdala and hypothalamus, increased signal intensity as arterial pressure declined. In contrast, arterial pressure elevation elicited smaller signal increases in medullary regions, the dorsolateral pons, and the right insula and signal declines in regions of the hypothalamus, with no change in deep cerebellar areas. Responses to both pressor and depressor challenges were typically lateralized. In a subset of animals, barodenervation resulted in rises and falls of blood pressure that were comparable to these resulting from the pharmacological challenges but different regional neural responses, indicating that the regional signal intensity responses did not derive from global perfusion effects but from baroreceptor mediation of central mechanisms. The findings demonstrate widespread lateralized distribution of neural sites responsive to blood pressure manipulation. The distribution and time course of neural responses follow patterns associated with early and late compensatory reactions.

SUMMARYIn eight mechanically ventilated patients in cardiogenic shock, we assessed the hemodynamic effects of an infusion of dopamine and dobutamine and evaluated its role in preventing the deleterious effects of administering each amine alone. Each patient received three infusions in a randomly assigned order: dopamine, 15 ,.tg/kg/min; dobutamine, 15 ,tg/kg/min; and a combination of dopamine, 7.S ,g/kg/min, and dobutamine, 7.5 ,ug/kg/min. Stroke volume index increased similarly with the three infusions, but dopamine alone increased oxygen consumption (p < 0.05 vs dobutamine alone and dopamine-dobutamine combined). The dopamine-dobutamine combination increased mean arterial pressure (p < 0.05 vs dobutamine), maintained pulmonary capillary wedge pressure within normal limits (p < 0.05 vs dopamine), and prevented the worsening of hypoxemia induced by dopamine (p < 0.05). The dopamine-dobutamine combination appears to be useful in the management of mechanically ventilated patients in cardiogenic shock.THE HEMODYNAMIC PICTURE of heart failure is characterized by a decrease in stroke volume and an increase in ventricular filling pressures. When acute pump failure is so severe that an adequate cardiac output cannot be maintained, hypotension supervenes despite the elevated peripheral resistance, and cardiogenic shock ensues. In this setting, diuretics and vasodilators cannot be used alone, and the therapeutic use of sympathomimetic amines such as dopamine and dobutamine is required.Dopamine, a precursor in the endogenous synthesis of norepinephrine, is a potent inotropic agent.I-1 It increases stroke volume both by a direct action and through the release of norepinephrine stores.4 When dopamine is used at a dose of 10-15 ig/kg/min, vasopressor effects appear. These effects are of particular value in patients with hypotension.5 However, an important side effect limits its use in cardiogenic shock: At a dose of 10 to 15 ,ug/kg/min, it may induce an increase in pulmonary capillary wedge pressure (PCWP). As a result, its use may be associated with pulmonary vascular congestion, arterial desaturation and increase in venous admixture.6 Dobutamine is also a potent inotropic agent that acts directly on adrenergic myocardial receptors without any release of norepinephrine from nerve endings.' In the treatment of severe heart failure, dobutamine induces an increase in cardiac output and stroke volume with a reduction of PCWP.6 In contrast to dopamine, dobutamine probably has minimal direct vascular activity even when it is used at higher dosages. However, a reduction in systemic arterial resistance (SAR), frequently accompanied by a slight fall in mean arterial pressure (MAP), generally occurs during dobutamine infusion in patients with chronic, low-output cardiac failure.8 This decrease in SAR may be due to a reduc- tion in compensatory vasoconstriction secondary to an improvement in stroke volume index (SVI). The aim of this study was to assess the efficacy of a combined dopamine-dobutamine infusion, 7.5 Ag/kgl min each, in t...

The cerebellar fastigial nuclei (FN) assist in regulating compensatory responses to large blood pressure changes and show structural injury and functional impairment to cardiovascular challenges in syndromes with sleep-disordered breathing. The patterned time course of FN responses to elevation or lowering of blood pressure and location of responsive regions within the nuclei are unclear. We evaluated FN neural activity in six anesthetized rats using optical imaging procedures during elevation and lowering of arterial pressure by phenylephrine and nitroprusside, respectively. Hypertension diminished optical correlates of FN neural activity, while measures of activity increased to hypotension, with peak neural responses occurring 5-10 s later than peak blood pressure changes. Blood pressure responses were followed by heart rate changes, and peak respiratory rates developed even later, in close temporal proximity to FN activity patterns. Although overall topographical response trends were similar, regional patterns of altered neural activity appeared to both hypertension and hypotension. The extent of neural change was greater during recovery from hypertension than for hypotension at high-dose levels. Blood pressure levels saturated with increasing phenylephrine doses, while FN activity continued to decline. No saturation appeared in heart or respiratory rate trends. The findings suggest that the FN compensate for large blood pressure changes by sympathoexcitatory and inhibitory processes, which accompany late-developing somatic or respiratory adjustments.

Ventral medullary surface (VMS) activity declines during rapid eye movement (REM) sleep, suggesting a potential for reduced VMS responsiveness to blood pressure challenges during that state. We measured VMS neural activity, assessed as changes in reflected 660-nm wavelength light, during pressor and depressor challenges within sleep/waking states in five adult, unrestrained, unanesthetized cats and in two control cats. Phenylephrine elevated blood pressure and elicited an initial VMS activity decline and a subsequent rise in VMS activity in all states, although the initial decline during quiet sleep occurred only in rostral placements. Phasic REM periods elicited a momentary recovery from the evoked activity rise, and arousals diminished the overall elevation in activity. A sodium nitroprusside depressor challenge increased VMS activity more in REM sleep than in quiet sleep, with the increase being even less in waking. Enhanced responses to depressor challenges during REM sleep suggest a loss of dampening of evoked activity during that state; state-related differential baroreflex sensitivity may result from sleep-waking changes in VMS responses to blood pressure challenges.