Perfused rat hearts were used to study the effects of acidosis on coronary tone. When pH was decreased, over the range pH 7.4 to pH 6.2, by reducing perfusate bicarbonate levels, under constant flow conditions, there was a transient decrease in coronary perfusion pressure (CPP), followed by a sustained acidosis-dependent increase in CPP, which reversed when pH was returned to pH 7.4. This increase in CPP was seen at perfusion rates of 5, 10, and 20 ml/min(-1). When using constant pressure perfusion acidosis reduced coronary flow. In a HEPES-buffered bicarbonate-free solution, acidosis did not cause a transient fall in CPP but it did produce a sustained increase in CPP. Addition of ammonium chloride (10 mM) reduced CPP, while washout of ammonium chloride increased CPP. The acidosis-induced increase in CPP was not affected by indomethacin, nitro-L-arginine, the nonselective adenosine receptor antagonist, 8-phenyl theophylline, or the thromboxane receptor antagonist, ZD 1542. The acidosis-induced increase in CPP was independent of the myocardial depressant effects of acidosis, but was attenuated by three different L-type calcium channel blockers. These results demonstrate that the coronary circulation of the rat constricts in response to acidosis. Experiments performed with L-type calcium channel blockers, and the calcium channel activator BAY K8644, suggest that constriction occurs via activation of L-type calcium channels. This would not be expected on the basis of electrophysiological studies, which have shown an inhibition of L-type calcium channels by acidosis.

We report evidence that a porphyrinic microsensor for detection of nitric oxide (NO) also detects biologically relevant concentrations of tyrosine (Tyr) in dog brain. Tyr is oxidized by this sensor at the same potential as NO, and the sensitivity for NO and Tyr are of the same order of magnitude. The interference from Tyr is of importance because 1) Tyr is abundant and 2) there is a concentration gradient of Tyr across the blood-brain barrier that can lead to unpredictable results if disturbed by ischemia or hypoxia. The knowledge of this interference is important for the interpretation of results obtained with this sensor and for the design of future studies.

No abstract

Cerebral venous outflow and carbon dioxide transients were studied during five different transitional states: (1) on and off 10% carbon dioxide breathing, (2) on and off hyperventilation, (3) on 7% carbon dioxide breathing, (4) on 10% carbon dioxide breathing initiated from 7% carbon dioxide breathing, and (5) on 10% carbon dioxide breathing initiated during intracarotid papaverine infusion, in pentobarbital anesthetized, paralyzed, mechanically ventilated dogs. Plots of the temporal relationships between these variables indicated that cerebral blood flow is closely related with cerebral venous carbon dioxide tension but not arterial carbon dioxide tension. The rate at which flow changed upon transition from one steady state to another was phase dependent, in that longer times were required to establish stable conditions in the on phase than in the off phase. The magnitude of the maximum rates of change in cerebral blood flow achieved during transition was influenced both by the size of the forcing function and the level of flow present at the time the response was initiated. Directional changes had no effect upon the maximum rate of the flow change as long as equivalent-sized forcing functions were employed and the initial blood flow levels were similar between responses. However, faster flow transients could be produced by increasing either of the latter two factors. These findings are consistent with the hypothesis that it is either tissue carbon dioxide tension or cerebral venous carbon dioxide tension that is the important variable regulated by cerebral blood flow. The rate-limiting factor in the response appears to be carbon dioxide delivery rate and not the rate of carbon dioxide diffusion.

The large increase in cerebral blood flow (CBF) after fluorocarbon (FC)-exchange transfusion is thought to be caused by low oxygen content, decreased viscosity, or direct vasodilatory effect of the FC perfusate. The aim of this study was to determine whether nitric oxide (NO)-mediated vasorelaxation is increased in FC-perfused hemoglobin (Hb)-free cats because NO is not scavenged by Hb. We measured regional CBF with radiolabeled microspheres in three groups of anesthetized mechanically ventilated cats. The first group [FC + N ω-nitro-l-arginine methyl ester (l-NAME); n = 7] underwent a complete FC-exchange transfusion with FC-43 and subsequent nitric oxide synthase (NOS) inhibition with l-NAME (10 mg/kg iv) followed by l-arginine (100 mg/kg iv). A second group (FC + saline; n = 6) underwent an identical protocol, but NOS was not antagonized (saline iv). In a third group (blood + l-NAME; n = 7), cats were not FC exchanged but NOS was inhibited. In a separate cohort of four FC-perfused cats, NOS activity in brain tissue samples was reduced to 26% of control after NOS inhibition. FC-exchange transfusion nearly doubled hemispheric blood flow in both FC-exchanged groups, whereas it was constant in the blood + l-NAME group. These increases in regional CBF (hemispheres, brain stem, cerebellum, thalamus, and white matter) were not reversed by inhibition of NOS, except in the neurohypophysis, wherel-NAME reduced blood flow to levels comparable to values in the blood +l-NAME group. In summary, increases in regional CBF after total FC-exchange transfusion are not caused by a lack of NO scavenging, with the exception of neurohypophysis. These findings suggest an increased vasorelaxation in neurohypophysis of FC-perfused and Hb-free cats caused by unscavenged NO, but this mechanism does not play a major role in FC-related CBF increases in the rest of the cerebral circulation.