Lorenz O. Lutherer

Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by hemorrhage or administration of endotoxin

The present studies were undertaken to determine if bilateral lesions of the fastigial nuclei of the cerebellum would impair the recovery and maintenance of mean arterial blood pressure during hypotension caused by hemorrhage or administration of endotoxin. We had shown previously that cerebellectomy would produce such an impairment, and the fastigial nuclei were implicated as the specific area involved due to the known pressor response observed when they are stimulated electrically. Chloralose-anesthetized dogs were made hypotensive by administration of E. coli endotoxin or hemorrhage to 50 mm Hg and observed over the subsequent 3 h. Dogs with fastigial nucleus lesions had a significantly lower mean arterial pressure during both the recovery and maintenance phases when compared with intact animals under both hypotensive protocols. In the hemorrhage study, a significant number of lesioned animals died whereas none of the controls died. Lesion of the fastigial nuclei produced an impairment similar to that seen with cerebellectomy. It is concluded that the fastigial nuclei play an important role in the recovery of blood pressure following a hypotensive episode.

The effects of chronic administration of naltrexone on appetite and water exchange in rats

The effects of chronic administration of naltrexone (200 microgram/kg/hr) on appetitive behaviors and renal water and electrolyte excretions were studied in rats. Naltrexone reduced food and water intake, the renal excretions of water and electrolyte excretions were studied in rats. Naltrexone reduced food and water intake, the renal excretions of water and electrolytes, and osmolar clearance. No changes in plasma levels of electrolytes, plasma and urine Na+-K+ ratios, hematocrit ratio, plasma osmolality, the clearances of K+ and Na+, and the reabsorption of solute free water were found. The changes in appetite were compensated for by appropriate changes in renal excretions, resulting in no change in electrolyte balance or water exchange. These observations are discussed in relation to current theories of the role of endorphins in appetite control.

Synergistic interactions between Ca2+ entries through L‐type Ca2+ channels and Na+–Ca2+ exchanger in normal and failing rat heart

We used confocal Ca2+ imaging and the patch‐clamp technique to investigate the interplay between Ca2+ entries through L‐type Ca2+ channels (LCCs) and reverse‐mode Na+–Ca2+ exchange (NCX) in activating Ca2+‐induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) in cardiac myocytes from normal and failing rat hearts. In normal myocytes exposed to N(6),2′‐O‐dibutyryl adenosine‐3′,5′‐cyclic monophosphate (db‐cAMP, membrane‐permeable form of cAMP), the bell‐shaped voltage dependence of cytosolic Ca2+ transients was dramatically broadened due to activation of SR Ca2+ release at high membrane potentials (30–120 mV). This broadening of Ca2+‐transient voltage dependence could be prevented by KB‐R7943, an inhibitor of the reverse‐mode NCX. Trans‐sarcolemmal Ca2+ entries were measured fluorometrically in myocytes during depolarizing steps to high membrane potentials. The total Ca2+ entry (ΔFTot) was separated into two Ca2+ entry components, LCC‐mediated (ΔFLCC) and NCX‐mediated (ΔFNCX), by exposing the cells to the specific inhibitors of LCCs and reverse‐mode NCX, nifedipine and KB‐R7943, respectively. In the absence of protein kinase A (PKA) stimulation the amplitude of the Ca2+‐inflow signal (ΔFTot) corresponded to the arithmetic sum of the amplitudes of the KB‐R7943‐ and nifedipine‐resistant components (ΔFTot=ΔFLCC+ΔFNCX). PKA activation resulted in significant increases in ΔFTot and ΔFLCC. Paradoxically, ΔFTot became ∼threefold larger than the sum of the ΔFNCX and ΔFLCC components. In myocytes from failing hearts, stimulation of PKA failed to induce a shift in Ca2+ release voltage dependence toward more positive membrane potentials. Although the total and NCX‐mediated Ca2+ entries were increased again, ΔFTot did not significantly exceed the sum of ΔFLCC and ΔFNCX. We conclude that the LCC and NCX Ca2+‐entry pathways interact synergistically to trigger SR Ca2+ release on depolarization to positive membrane potentials in PKA‐stimulated cardiac muscle. In heart failure, this new form of Ca2+ release is diminished and may potentially account for the compromised contractile performance and reduced functional reserve in failing hearts.

Inhibitory effects of cerebellar lesions on respiration in the spontaneously breathing, anesthetized cat

Acute cerebellectomy depressed spontaneous respiration in cats anesthetized with chloralose-urethane. After cerebellectomy there was an increased interbreath interval (TTOT) accompanied by increased inspiratory and expiratory durations (TI and TE, respectively). However, the change of TE exceeded that of TI so that TI/TTOT decreased. Tidal volume (VT) and mean inspiratory flow (VT/TI) were not affected. No respiratory variable was significantly altered when cerebellectomy was performed subsequent to bilateral vagotomy. Bilateral lesions of the rostral fastigial nuclei (FN) in cats with intact vagi also caused a reduction in ventilation due to increased TTOT. In this case TI and VT/TI increased, but VT and TI/TTOT remained unchanged. Bilateral control lesions that usually included portions of the dentate nuclei did not influence respiration. The results suggest that in the anesthetized cat the cerebellum tonically excites respiratory centers controlling respiratory rate and the termination of inspiration. A part of this influence may be mediated by the rostral FN. In addition, vagal input appears to be important in the expression of the cerebellar influence on spontaneous respiration.

Lack of central effects of peripherally administered adenosine A1 agonists on synaptic transmission in the rat hippocampus

Peripheral administration of adenosine A(1) receptor selective agonists is generally thought to protect the hippocampus against ischemic damage via central actions. We examined the effects of two peripherally administered A(1) agonists, cyclohexyladenosine (CHA) and adenosine amine congener (ADAC), on synaptic transmission in the hippocampus and on indices of cardiovascular function. We conclude that the permeability of these agonists is not sufficient to result in concentrations necessary to activate central adenosine A(1) receptors within the hippocampus.

Academia, Investigator-Initiated Research, and a Unique Resource to Support Both

Scholarly activity is an important expectation of an academic institution, and the requirements for it as part of the education and training of medical students and residents continue to increase. Investigator-initiated research is a major component of scholarly activity. However, clinical faculty have little or no protected time for research. The administration at the Texas Tech University Health Sciences Center addressed this problem with a unique approach by creating an institute to support faculty research.