Role of alpha-1 adrenoceptor subtypes mediating constriction of the rabbit ear thermoregulatory microvasculature.

An acute in vivo preparation of the microvasculature of the rabbit ear was used to evaluate the functional role of alpha1 (alpha1)-adrenoceptor subtypes in thermoregulatory microcirculation. The effect of alpha1-adrenoceptor subtype blockade on phenylephrine-induced vasoconstriction was assessed with the alpha1A, alpha1B, and alpha1D-adrenoceptor-selective antagonists 5-methyl-urapidil (10(-8) M), chloroethylclonidine (10(-5) M), and 8-[2-[4(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4.5]deca ne-7,9-dione dihydrochloride (BMY7378) (10(-6) M), respectively. The results demonstrated that pretreatment of the ear microvasculature with 5-methyl-urapidil or BMY7378 shifted the phenylephrine concentration-response curve rightward and significantly changed the log of the phenylephrine concentration, causing half-maximum stimulation (EC50) in arterioles (p < 0.05). BMY7378 shifted the phenylephrine concentration-response curve of the arteriovenous anastomoses about 100-fold rightward (p < 0.05). All three alpha1-adrenoceptor antagonists eliminated the vasoconstrictive effects of phenylephrine on venules. The results indicate that the ear microvasculature has a heterogenous distribution of alpha1-adrenoceptor subtypes. The alpha1A and alpha1D-adrenoceptor subtypes appear to have a greater influence on constrictive function in arterioles, whereas the alpha1D-adrenoceptor is the dominant constrictor of arteriovenous anastomoses. In general, the alpha1-adrenoceptor does not play a major vasoconstrictor role in venules. Chloroethylclonidine, an irreversible alpha1B-adrenoceptor antagonist, induced contractile responses in the ear microvasculature, probably due to its alpha2-adrenoceptor agonist effects. This study extended our understanding of the adrenergic receptor control mechanisms of a cutaneous thermoregulatory end organ characterized by two parallel perfusion circuits providing nutritional and thermoregulatory functions.

Effects of dexamethasone on the contractile function of reperfused skeletal muscle.

This study evaluated the effects of dexamethasone (DXM) on contractile function of reperfused extensor digitalis longus (EDL) muscles following 3-hour ischemia and 24-hour reperfusion. The rats were divided into four groups: normal muscle, ischemia with saline treatment, ischemia/reperfusion with saline treatment, and ischemia/reperfusion with DXM treatment groups. DXM (0.6 mg kg[-1]) or saline (3.0 ml kg[-1]) was administered at 3 hours prior to ischemia. Results showed that although contractile force in all three treated groups was significantly lower than that of normal EDL, the average isometric tetanic contractile force in the DXM-treated group was significantly greater than that in the saline-treated ischemia and ischemia/reperfusion groups. A significant difference was also seen at the peak force and at 5 seconds of the fatigue trains, and with a longer fatigue half-time (FT1/2) in the DXM-treated group than in the other two groups. Histologically, edema, inflammation and necrosis of muscle fiber were less severe in the DXM-treated group than in the saline-treated group. The results indicate that pretreatment with DXM appears to attenuate, but does not completely reverse, the contractile function deficit of ischemic skeletal muscle during the first 24 hours of reperfusion.

Effects of donor characteristics and platelet in vitro time and temperature on platelet aggregometry.

PURPOSE: This study was undertaken to determine whether platelet donor characteristics and the duration and temperature of platelet storage affect platelet aggregation. METHODS: Half of each platelet-rich plasma sample, obtained from 42 healthy volunteers, was maintained at 37 degrees C and the other half at 25 degrees C. Aggregation was stimulated with adenosine diphosphate (ADP), epinephrine, or collagen 1, 2, 4, and 6 hours after platelet donation. The lag time, slope of the aggregation curve, and percent peak aggregation were determined for each aggregation test. RESULTS: Age, sex, time of donation, smoking status, estrogen replacement, and menstruation did not significantly influence platelet aggregation. Storage time and temperature had a major influence on platelet reactivity, with the reactivity decreasing with prolonged storage and higher storage temperatures. Peak ADP-induced aggregation for platelets stored at 37 degrees C was significantly less (p < 0.0002) than the values obtained for ADP aggregation at 25 degrees C. Collagen-stimulated peak aggregation of platelets maintained at 37 degrees C for 4 and 6 hours was also significantly less than the corresponding values at 25 degrees C. Epinephrine-stimulated aggregation produced similar results, with peak platelet aggregation decreasing with time (50.3% +/- 2.9% at 6 hours compared with 38.5% +/- 3.7% at 2 hours at 25 degrees C) and high storage temperatures (there was less aggregation by platelets stored at 37 degrees C at each time period studied). CONCLUSIONS: It is recommended that platelet-rich plasma for platelet aggregation testing be maintained at room temperature and be used between 2 and 4 hours after platelet donation.

Contractile and metabolic function following an ischemia-reperfusion injury in skeletal muscle: influence of oxygen free radical scavengers.

Skeletal muscle contraction and metabolism was evaluated using an in vivo, intact autoperfused canine hindlimb model during 7 hours of reperfusion following 4 hours of complete ischemia, with and without bolus administration of superoxide dismutase (SOD) and catalase (CAT) at the start of reperfusion. Contractile tension of paw dorsiflexion during reperfusion demonstrated small but statistically non-significant increases of recovery towards pre-ischemic baseline with SOD/CAT (i.e. 43% +/- 10 vs 32% +/- 9 with muscle-stimulated tetanic tension). Oxygen utilization by the hindlimb rose during reperfusion from a baseline in the control group of 2.4 +/- 0.3 ml 02/min to 5.4 +/- 1.1 during the first 10 minutes and plateaued at 3.5 +/- 1.3 by the first hour with no differences in the SOD/CAT group. Lactate clearance was prompt (increase from a pre-ischemia value of zero to 0.93 +/- .14 mM/min by 5 minutes and return to near-zero by 1 hour in controls) exhibiting no sustained anaerobic metabolism and was not affected by SOD/CAT. These finding demonstrate irreversible loss of 60-70% of skeletal muscle contraction with preservation of aerobic metabolic capacity at 225% of basal activity. Bolus administration of SOD/CAT at the start of reperfusion offered no significant improvement in metabolic or contractile function. These observations, in a model simulating the in vivo setting, necessitate evaluating alternate ischemia reperfusion conditions and modified free-radical inhibitor protocols before any clinical benefit can be assumed.