Influence of hypercapnic vasodilation on cerebrovascular autoregulation and pial arteriolar bed resistance in piglets

Abstract

Changes in both pial arteriolar resistance (PAR) and simulated arterial-arteriolar bed resistance (SimR) of a physiologically based biomechanical model of cerebrovascular pressure transmission, the dynamic relationship between arterial blood pressure and intracranial pressure, are used to test the hypothesis that hypercapnia disrupts autoregulatory reactivity. To evaluate pressure reactivity, vasopressin-induced acute hypertension was administered to normocapnic and hypercapnic (N = 12) piglets equipped with closed cranial windows. Pial arteriolar diameters were used to compute arteriolar resistance. Percent change of PAR (%DeltaPAR) and percent change of SimR (%DeltaSimR) in response to vasopressin-induced acute hypertension were computed and compared. Hypercapnia decreased cerebrovascular resistance. Indicative of active autoregulatory reactivity, vasopressin-induced hypertensive challenge resulted in an increase of both %DeltaPAR and %DeltaSimR for all normocapnic piglets. The hypercapnic piglets formed two statistically distinct populations. One-half of the hypercapnic piglets demonstrated a measured decrease of both %DeltaPAR and %DeltaSimR to pressure challenge, indicative of being pressure passive, whereas the other one-half demonstrated an increase in these percentages, indicative of active autoregulation. No other differences in measured variables were detectable between regulating and pressure-passive piglets. Changes in resistance calculated from using the model mirrored those calculated from arteriolar diameter measurements. In conclusion, vasodilation induced by hypercapnia has the potential to disrupt autoregulatory reactivity. Our physiologically based biomechanical model of cerebrovascular pressure transmission accurately estimates the changes in arteriolar resistance during conditions of active and passive cerebrovascular reactivity.

Fig. 1.

Histograms of percent change in pial arteriolar resistance (%ΔPAR) and percent change in simulated arterial-arteriolar resistance (%ΔSimR). Pressor challenge causes an increase of arterial blood pressure and a change in PAR and SimR. Hatched bars represents hypercapnia, and solid bars represents normocapnia. A: histogram of %ΔPAR. B: histogram of %ΔSimR. By application of both the Shapiro-Wilks and Kolmogorov-Smirnov tests, both distributions were determined not to be normally distributed, with respective levels of significance of P < 0.007 and P < 0.001.

Fig. 2.

%ΔPAR and %ΔSimR induced by vasopressin-induced acute hypertensive challenge vs. percent change of cerebral perfusion pressure (%ΔCPP). A: vasopressin-induced hypertension challenge during normocapnia for all preparations. Hatched bar graph represents mean %ΔPAR (±SE), and solid bar represents %ΔSimR (±SE). For all preparations (N = 12), hypertensive challenge during normocapnia caused pial arteriolar vasoconstriction and increased simulated cerebrovascular resistance. B: vasopressin-induced hypertension challenge during hypercapnia for the intact autoregulation group (N = 6). For this group, hypertensive challenge caused pial arteriolar vasoconstriction and increased simulated cerebrovascular resistance. C: vasopressin-induced hypertension challenge during hypercapnia for the pressure passive group (N = 6). For this group, hypertensive challenge caused pial arteriolar vasodilation and decreased cerebrovascular resistance (N = 6). Intragroup comparisons of mean of %ΔPAR and %ΔSimR were not different, whereas intergroup comparisons of %ΔPAR and %ΔSimR were significantly different.