Decreased calcium accumulation in isolated nerve endings during hibernation in ground squirrels.

Resting and depolarization-induced 45CaCl2 accumulation was compared for synaptosomes isolated from hibernating and nonhibernating ground squirrels. Channel subtype antagonists were used to identify the active voltage-sensitive calcium channel subtypes in these preparations. There was significantly less 45Ca2+ accumulation in synaptosomes isolated from hibernating as compared to cold-adapted nonhibernating ground squirrels in both basal (p < 0.005) and depolarizing (p < 0.03) media over a 30 sec to 5 min incubation period. The elevation in 45Ca2+ accumulation triggered by K+ depolarization was blocked by 50 microM CdCl2, 1 microM omega-conotoxin MVIIC or 1 microM omega-agatoxin IVA. Inhibition was not observed with 1 microM nifedipine or with 1 microM omega-conotoxin GVIA. These results suggest that hibernation is associated with reduced presynaptic 45Ca2+ conductance via voltage-sensitive channels with a pharmacological sensitivity that is different from the established L-, N-, and P-types in other systems but share features of the recently described Q-type calcium channel. This decrease may reflect a cellular adaptation that helps confer tolerance to the near total cerebral ischemia associated with hibernation.

Antagonists of excitatory amino acids and endogenous opioid peptides in the treatment of experimental central nervous system injury.

Trauma to the central nervous system can lead to primary injuries occurring at the time of impact as well as secondary or delayed injury processes that can result from cellular hypoxia, oligemia/ischemia, edema and swelling, and intracranial hypertension that are manifested over a period of hours to weeks after the initial event. Although the mechanisms underlying delayed tissue injury are poorly understood, they appear to be associated with endogenous neurochemical changes resulting from traumatic nervous system injury. These neurochemical changes may include excessive neurotransmitter release, deregulation of ion homeostasis, and the synthesis, release, or activation of various "autodestructive" neurochemical factors. Experimental studies over the past decade indicate that these alterations mediate important components of the neurochemical cascade leading to central nervous system injury. Furthermore, pharmacologic manipulations of these neurochemical changes have been reported to attenuate secondary central nervous system damage, ameliorate neuronal death, and promote functional recovery after central nervous system injury. This article focuses on the role of excitatory amino acid neurotransmitters, endogenous opioid peptides, and magnesium in the pathophysiology of central nervous system injury and on the therapeutic manipulation of these systems to improve functional outcome after central nervous system injury.

Effects of arterial and venous volume infusion on coronary perfusion pressures during canine CPR.

Intraarterial (IA) volume infusion has been reported to be more effective than intravenous (IV) infusion in treating cardiac arrest due to exsanguination. A rapid IA infusion was felt to raise intraaortic pressure and improve coronary perfusion pressure (CPP). The purpose of this study was to determine if IA or IV volume infusion could augment the effect of epinephrine on CPP during CPR in the canine model. Nineteen mongrel dogs with a mean weight of 26.3 +/- 4.2 kg were anesthetized and mechanically ventilated. Thoracic aortic (Ao), right atrial (RA) and pulmonary artery catheters were placed for hemodynamic monitoring. Additional Ao and central venous catheters were placed for volume infusion. Ventricular fibrillation was induced and Thumper CPR was begun after 5 min (t = 5). At t = 10, all dogs received 45 micrograms/kg IV epinephrine. Six animals received epinephrine alone (EPI). Five dogs received EPI plus a 500 cc bolus of normal saline over 3 min intravenously (EPI/IV). Another group (n = 8) received EPI plus the same fluid bolus through the aortic catheter (EPI/IA). Resuscitation was attempted at t = 18 using a standard protocol. There was a significant increase in CPP over baseline in all groups. The changes in CPP from baseline induced by EPI, EPI/IV and EPI/IA were 20.6 +/- 3.7, 22.8 +/- 4.2 and 22.2 +/- 2.4 mmHg, respectively. Volume loading did not augment the effect of therapeutic EPI dosing. By increasing both preload and afterload, volume administration may in fact be detrimental during CPR.

Effect of epinephrine on end-tidal carbon dioxide monitoring during CPR.

End-tidal carbon dioxide (ETCO2) has been shown to correlate with coronary perfusion pressure (CPP) during CPR and has been proposed as a useful noninvasive monitor of CPR efficacy. The effects of therapeutic epinephrine dosing on ETCO2 and CPP in six dogs were examined. Ventricular fibrillation was induced and left untreated for five minutes before CPR was initiated. After five minutes of CPR, epinephrine 0.045 mg/kg IV was administered. CPP and ETCO2 were compared immediately before and two minutes after epinephrine administration. There was a significant increase in CPP from 12.2 +/- 9.6 to 26.8 +/- 7.1 mm Hg (P = .006) after epinephrine. This was accompanied by a significant decrease in ETCO2 from 8.2 +/- 2.9 to 3.8 +/- 2.0 mm Hg (P = .01). These data indicate that after epinephrine administration, caution must be exercised in using ETCO2 as an indicator of CPP.