The use of naloxone (NAL), an opioid receptor antagonist, has provided indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. To determine if endogenous opioids act centrally to influence cardiovascular function, injections of D-Ala2-Met-enkephalinamide (DAME), a potent Met-enkephalin analog, were made into the 3rd cerebral ventricle (ICV) of 5 conscious cynomulgus monkeys restrained in primate chairs. Systolic blood pressure (SBP) and heart rate (HR) were determined every 10 min during a 30-60 min control period and for up to 5 hr post-injection. Colonic temperature (Tc) was monitored continuously. SBP declined from baseline values with 50 and 100 micrograms (85.2 and 170.4 nM) doses but was significant (p less than 0.001) for only the 100 micrograms dose between 15-125 min post-injection. HR also decreased but did not exhibit any significant variation with time. However, when averaged across time, HR fell significantly (p less than 0.001) from baseline: -9.1 +/- 2.3 and -15.0 +/- 2.1 b/min for 50 and 100 micrograms DAME, respectively. Tc displayed a nonsignificant, delayed (greater than 2 hr) rise in Tc with the 50 micrograms dose, whereas the 100 micrograms dose caused a significant (p less than 0.001) decline in Tc (from 65-125 min post-injection). NAL injected ICV attenuated the effects of DAME but had no effect on SBP, HR or Tc when injected alone. Systemic injection of DAME (300 micrograms) in one monkey produced a transient decline in SBP (26 mmHg within 2 min) which returned to baseline values 4 min post-injection. HR and Tc were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Effects of opiate receptor drugs injected intracerebrally into the normovolemic and hypovolemic monkey.

Systemic injection of naloxone (NAL), an opioid-receptor antagonist, significantly elevates systolic blood pressure (SBP) in anesthetized hypovolemic monkeys, providing indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. The purpose of this study was to identify specific centrally located opioid receptor sites that participate in SBP regulation under normovolemic and hypovolemic conditions. In 6 monkeys, bilateral guide cannulae were stereotaxically implanted above areas ranging from the diencephalon to the lower medulla. Microinjections (1 microliter) of D- Ala2-Met-enkephalinamide (DAME) (3.4-27.2 nM) into normovolemic unanesthetized monkeys reduced SBP by 10-65 mm Hg in a dose-related fashion. Subsequent injection of NAL (12.2 nM) attenuated this hypotensive response. Heart rate fell 20-40 bpm with DAME, but not in response to dose. In the anesthetized animal rendered hypotensive (SBP = 45 mm Hg) by hemorrhage. NAL injected into predetermined DAME-sensitive sites failed to increase SBP more than 5 mm Hg. Even consecutive injections into multiple sites elevated SBP only 20 mm Hg. We conclude that the centrally located opioid-sensitive sites tested exert only a mild influence in mediating hemorrhagic hypotension.

Animals↗

PubMedDate not supplied

A magnetically actuated left ventricular assist device.

Over the past 6 years, research has led to development of a small, lightweight, power-efficient, uniquely simple ventricular assist device driven by a magnetic actuator. Magnetic actuation permits total elimination of all mechanical motion converter components used for pusher plate displacement, resulting in a significant reduction in complexity and resultant increase in reliability. Extensive in vitro mock loop development has resulted in a left ventricular assist device (LVAD), the primary design parameters of which for the clinical prototype actuator and pump are 1) an actuator weight of 312 g, 2) actuator size of 32.5 cm3, 3) power requirements of 7.8 to 11.4 watts (60-100 beats per minute [BPM]), and 4) system efficiency of 24% to 34% and average dynamic stroke volume of 65 ml. Initial in vivo tests assessed this LVAD's performance in four sheep under three acute conditions of ventricular dysfunction. The results demonstrate that, at a pump-rate of 100 BPM, mean aortic pressure increased by 45-50 mmHg during 1) beta blockade, 2) coronary ligation, and 3) ventricular fibrillation. Pump flow ranged from 2.71 L/min to a maximum of 4.6 L/min. Acute test periods were arbitrarily set for 6 hours duration. Of the four sheep, two survived, one lived 5 hours, and the fourth lived 4.5 hours. Global fibrillation was the primary cause of failure. This initial in vivo data demonstrates the pump's ability to maintain satisfactory hemodynamic parameters of flow and pressure under three acute conditions of extreme left ventricular dysfunction in an animal model. These initial LVAD performances were encouraging. Further tests will use calves with a greatly expanded performance evaluation protocol.

Adrenergic beta-Antagonists↗