Group B streptococcal sepsis impairs cerebral vascular reactivity to acute hypercarbia in piglets.

We investigated whether group B streptococcal (STREP) infusion impairs the cerebral blood flow (CBF) response to acute hypercarbia in piglets, and whether STREP-induced prostanoids or hemodynamic alterations could account for this impairment. Piglets, 2-3 wk old, were anesthetized, paralyzed, and mechanically ventilated (50% O2; partial pressure of arterial CO2 (PaCO2) approximately 40 torr). CBF was assessed by internal carotid artery blood flow (ICBF). Group 1 (n = 5) received a continuous infusion of STREP for 4 h (2.0-8.0 x 10(7) org/kg-min). Group 2 (n = 5) was pretreated with indomethacin (5 mg/kg), then received the identical STREP infusion. Group 3 (n = 6) did not receive STREP, but cardiac output (CO) and systemic blood pressure (BP) were reduced to levels equal to that of group 1 by incremental inflation of a left atrial balloon (LAB) catheter. Cerebral vascular reactivity to acute hypercarbia (PaCO2 approximately 70 torr for 7.5 min) was assessed at baseline and after each hour of STREP infusion or LAB inflation. We found that 4 h of STREP infusion caused CO to fall significantly (634 +/- 121 to 324 +/- 172 mL/min, group 1; 600 +/- 68 to 291 +/- 80 mL/min, group 2) and BP to fall significantly (104 +/- 20 to 57 +/- 4 mm Hg, group 1; 91 +/- 11 to 53 +/- 16 mm Hg, group 2) By design, in group 3 LAB inflation caused CO (573 +/- 181 to 375 +/- 159 mL/min) and BP (104 +/- 14 to 60 +/- 9 mm Hg) to fall to values not significantly different from septic groups 1 and 2. At 4 h, unilateral ICBF decreased significantly during STREP infusion in group 1 (32.0 +/- 10.8 to 21.0 +/- 7.3 mL/min) and group 2 (22.9 +/- 9.9 to 13.1 +/- 4.3 mL/min), but not in nonseptic group 3 (23.1 +/- 7.4 to 19.6 +/- 6.3 mL/min). At baseline, hypercarbia induced an increase in ICBF (% delta ICBF = 68.7 +/- 13.0% in group 1, 62.2 +/- 15.6% in group 2, and 87.7 +/- 34.0% in group 3). After 4 h of STREP, this response was completely ablated as ICBF fell during hypercarbia by -7.8 +/- 23.2% (group 1). Indomethacin did not protect cerebral vascular reactivity after 4 h of STREP infusion, as % delta ICBF fell during hypercarbia by -10.9 +/- 17.7% (group 2). In contrast, despite equivalent reductions in CO and BP after 4 h of LAB inflation in nonseptic group 3, ICBF rose during hypercarbia by 61.8 +/- 23.2%, not significantly different from baseline, but significantly different from the decrease in % delta ICBF in groups 1 and 2. We conclude that STREP infusion reduces ICBF and cerebral vascular reactivity to acute hypercarbia in piglets. This phenomenon is not accounted for by STREP-induced reduction in CO or BP, and is not mediated by prostanoids.

Relationship between oxygen delivery and metabolic acidosis during sepsis in piglets.

OBJECTIVE: To determine if the preservation of oxygen delivery (DO2) ameliorates the development of metabolic acidosis during group B streptococcal infusion. METHODS: We examined 22 piglets (2 to 4 wks of age) that were anesthetized, intubated, and mechanically ventilated. Three groups of piglets were studied: group 1 (n = 6), in which DO2 was reduced progressively over 4 hrs by infusion of group B streptococci; group 2 piglets (n = 6) received a similar infusion of streptococci, but DO2 was preserved at presepsis levels by the infusion of dextran and exogenous porcine RBCs; group 3 piglets (n = 6) received no bacteria, but did receive a continuous infusion of 0.9% sodium chloride to maintain cardiac output, and thus, DO2, at baseline levels. To correlate arterial lactate concentrations with metabolic acidosis, four additional piglets received the continuous infusion of streptococci. RESULTS: DO2 decreased significantly in group 1 (14.2 to 5.7 mL oxygen/kg/min) but not in either group 2 or 3. The arterial pH decreased significantly in both septic groups, groups 1 and 2 (7.47 to 7.20; 7.45 to 7.36, respectively), but not in the uninfected group 3. The pH was significantly lower for group 1 vs. group 2 piglets at 210 and 240 mins of streptococcal infusion. Base excess decreased significantly for group 1 and group 2 piglets (+1.5 to -13.9; -0.1 to -5.8 mM/L, respectively) but not in group 3. Base excess was significantly lower for group 1 vs. group 2 piglets at 210 and 240 mins of streptococcal infusion. Oxygen extraction increased significantly for only the low DO2 group 1 piglets (32% to 73%), and did not differ comparing group 2 vs. group 3. In both groups of septic piglets, metabolic acidosis developed before any detectable reduction in oxygen consumption. The increase in circulating lactate concentration (1.0 to 4.6 mM/L) was correlated with the decrease in base excess (-1.0 to -9.7 mM/L) in the four additional piglets that received an infusion of streptococci. CONCLUSIONS: Maintaining DO2 at presepsis levels ameliorated the development of metabolic acidosis during streptococcal infusion. Nevertheless, a significant degree of metabolic acidosis developed despite the preservation of DO2.

Internal jugular venous oxygen saturation does not reflect sagittal sinus oxygen saturation in piglets.

Can blood samples from the internal jugular vein (IJ) be used reliably in place of sagittal sinus (SS) samples in the calculation of cerebral oxygen extraction? To test this question we compared the O2 saturation (Sat) of blood samples drawn from SS, IJ vein, and pulmonary artery (MV) during hypercarbia, eucarbia and hypocarbia in 7 paralyzed, ventilated piglets. Cerebral blood flow was assessed by measuring unilateral internal carotic artery blood flow (ICABF), determined by an electromagnetic flow probe placed around the common carotid artery after ligation of the external carotid artery. During hypocarbia, eucarbia and hypercarbia SatSS (37.3 +/- 9.3, 48.9 +/- 10.2, 70.8 +/- 11.8%, respectively) was significantly different from SatIJ (54.8 +/- 8.9, 54.5 +/- 9.0, 62.0 +/- 15.1%) and SatMV (55.9 +/- 5.5, 58.7 +/- 5.3, 53.5 +/- 11.2%). The mean slope of the SatSS vs. PaCO2 regression lines was +0.583 +/- 0.303%/mm Hg, significantly greater than the mean slope of the regression lines for SatIJ vs. PaCO2 (+0.087 +/- 0.310%/mm Hg) or SatMV vs. PaCO2 (-0.112 +/- 0.230%/mm Hg). The relationship of ICABF vs. PaCO2 (mean slope = 0.444 +/- 0.294 ml/min/mm Hg) was statistically significant, while the relationship of cardiac output (determined by an electromagnetic flow probe placed around the pulmonary artery) vs. PaCO2 (mean slope = 0.470 +/- 1.617 ml/min/mm Hg) was not. We conclude that blood samples from the IJ do not reliably reflect cerebral venous blood and cannot be substituted for SS samples in piglets. It is most probable that the substitution of IJ for SS blood is not valid in piglets because the IJ receives venous effluent from noncerebral tissue.

Effects of dextran infusion on cardiac output, oxygen delivery, and oxygen utilization in piglets during the first month of life.

We determined the effects of volume infusion on cardiac output, oxygen delivery (Do2), oxygen consumption (Vo2), and oxygen extraction (O2 extr) in piglets at ages 5 to 14 days and 3 to 5 wk. Eighteen piglets were anesthetized, intubated, and mechanically ventilated. Six piglets (5 to 14 days old) and six piglets (3 to 5 wk old) received iv dextran (MW 70,000 daltons; 30 to 40 ml/kg) sufficient to raise mean left atrial pressure (LAP) from approximately 4 to 15 mm Hg over 30 min. Six piglets received 0.9% NaCl at 4 ml/kg.h to maintain LAP constant at 4 mm Hg over a 30-min period. All piglets receiving dextran had increased cardiac output (mean elevation 39 +/- 16 [SD]%; range +19% to +73%; p less than .005). This response was mediated entirely by an elevation in stroke volume, as heart rate did not change significantly. However, all piglets receiving dextran reduced Hgb concentration (10.1 +/- 1.5 to 7.5 +/- 1.4 g/dl, p less than .001), a decrease which completely offset the increase in cardiac output. Consequently, Do2 did not increase after dextran infusion (17.4 +/- 1.8 to 18.4 +/- 2.8 ml/min.kg). Neither Vo2 nor O2 extr changed significantly after dextran. No differences were noted in the response to dextran infusion comparing 5 to 14-day-old piglets with 3 to 5-wk-old piglets. Unlike fetal lambs, newborn piglets are able to elevate cardiac output significantly in response to volume loading. However, if these data can be extrapolated to human infants, volume infusion without concurrent blood transfusion is likely to increase systemic cardiac output but not improve Do2.

Neither nitroglycerin nor nitroprusside selectively reduces sepsis-induced pulmonary hypertension in piglets.

No therapeutic agent consistently decreases pulmonary arterial pressure (PAP) more than aortic pressure in neonates with persistent pulmonary hypertension of the newborn. We have investigated whether nitroglycerin (NG) or nitroprusside (NP) selectively decreases PAP in an animal model of sepsis-induced pulmonary hypertension. Piglets were anesthetized, intubated, and ventilated. Pulmonary hypertension was induced by an iv infusion of group B Streptococci. Piglets were then divided into three groups with group B Streptococci infusion ongoing. Neither PAP nor the pulmonary vascular resistance index was decreased significantly by either NP or NG. NP decreased significantly both mean aortic pressure and the systemic vascular resistance index. Cardiac index decreased significantly during both NG and placebo infusion. These data suggest that neither NP nor NG is likely to be beneficial in sepsis-induced pulmonary hypertension in newborns.

Oxygen delivery, oxygen consumption, and metabolic acidosis during group B streptococcal sepsis in piglets.

The development of metabolic acidosis during neonatal sepsis with group B streptococci (GBS) has been attributed to progressive tissue ischemia resulting from reduced oxygen delivery (QO2). Using an animal model of GBS disease, we attempted to test this hypothesis by comparing the development of metabolic acidosis in two groups of piglets with comparably diminished systemic QO2, one septic and one not. Eighteen anaesthetized piglets were instrumented to observe aortic pressure, cardiac output, arterial and mixed venous blood gases, oxygen content, and hemoglobin concentration. QO2, oxygen consumption, and oxygen extraction ratio were calculated. Six piglets (group 1) received continuous infusion of live GBS organisms; six piglets (group 2) received continuous infusion of phenylephrine (PE), beginning with 10-micrograms/kg/min and increasing as required to match the PE-induced reduction in QO2 to the fall observed in the group 1 (GBS) piglets at each 30-min interval. Group 3 piglets (n = 6) received 0.9% saline and served as controls. No differences in either cardiac output or QO2 were noted comparing GBS and PE piglets at any time interval from 0-180 minutes. At 120, 150, and 180 minutes, both QO2 and cardiac output were lower in GBS and PE piglets compared to controls. Despite equivalent reductions in cardiac output and QO2, only GBS piglets developed significant metabolic acidosis, while pH and base deficit for PE piglets did not differ from controls. Oxygen consumption did not differ significantly among the three experimental groups at any observation time. Oxygen extraction ratio did not differ comparing PE and GBS piglets at any observation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective elevation of systemic blood pressure by epinephrine during sepsis-induced pulmonary hypertension in piglets.

In a piglet model of group B beta Streptococci (GBS)-induced pulmonary hypertension, we have determined hemodynamic responses to epinephrine (EPI) infusion in both the systemic and pulmonary circulations. Three groups of piglets (GBS + EPI, n = 6; GBS + placebo, n = 6; placebo, n = 6) were studied. GBS, infused intravenously at approximately 5 X 10(7) organisms/kg/min, reduced cardiac index and stroke volume index while elevating pulmonary artery pressure and pulmonary vascular resistance index. Systemic vascular resistance index, heart rate and aortic pressure did not change during GBS infusion. Six piglets received intravenous EPI after cardiac index had fallen by 30% during GBS infusion. At 3.5, 7.0, and 15 micrograms/kg/min, respectively, EPI raised aortic pressure by 18.5, 31.0, and 45.0 mm Hg while EPI reduced pulmonary artery pressure by 5.2, 6.3, and 8.2 mm Hg. At each dose, EPI elevated systemic vascular resistance index and lowered pulmonary vascular resistance index. At 3.5 micrograms/kg/min, the elevation of aortic pressure was associated with an increase in both cardiac index and systemic vascular resistance index. At higher EPI doses, the rise in aortic pressure was accounted for entirely by an increase in systemic vascular resistance index. Systemic acid/base status and PaO2 did not differ among piglets who received GBS + EPI, GBS alone, or placebo. Extrapolation of these data to human infants must be approached with extreme caution. However, selective elevation of systemic blood pressure may be a feasible strategy for some infants to impede right-to-left shunting of blood often associated with sepsis-induced pulmonary hypertension.

Effects of phenylephrine on systemic and pulmonary artery pressure during sepsis-induced pulmonary hypertension in piglets.

The effects of intravenous phenylephrine (PE) on aortic blood pressure (AOP), pulmonary artery pressure (PAP), and cardiac output (CO) were evaluated in piglets with normal PAP and piglets with sepsis-induced pulmonary hypertension. Anesthetized, ventilated piglets (1-4 weeks; n = 22) were divided into four groups - group 1 (n = 5) received group B beta streptococci (GBS) followed by PE (300 micrograms/kg); group 2 (n = 6) received GBS alone; group 3 (n = 6) received placebo infusion; group 4 (n = 5) received PE alone (300 micrograms/kg). Infusion of GBS in piglets (groups 1 and 2) elevated PAP by 149 and 176%, reduced CO by 34 and 28%, and did not affect AOP. Administration of PE (groups 1 and 4) raised AOP by 30 and 27% without significantly affecting PAP. However, CO fell after PE by 31 and 39%, respectively. If selective elevation of systemic blood pressure is to become an effective strategy for human newborns with right-to-left shunts caused by sepsis-induced pulmonary hypertension, agents other than PE, with less associated reduction of CO, need to be identified.