Early and late hemodynamic consequences of group B beta streptococcal sepsis in piglets: effects on systemic, pulmonary, and mesenteric circulations.

We have modified our previously described experimental model of neonatal sepsis using group B beta hemolytic streptococci (GBS) in piglets and report here early and late hemodynamic responses to GBS infusion in the systemic, pulmonary, and mesenteric circulations. Piglets were anesthetized, intubated, and ventilated. Aortic blood pressure (AOP), pulmonary artery pressure (PAP), central venous pressure (CVP), left atrial pressure (LAP), cardiac index (CI), mesenteric blood flow index (MBFI), and heart rate (HR) were measured directly. Systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), mesenteric vascular resistance index (MVRI), and stroke volume index (SVI) were calculated. Sepsis was induced by continuous IV infusion of live GBS beginning at 0.5 X 10(7) organisms/kg/min. LAP was held constant throughout the sepsis protocol. PAP and PVRI were the most sensitive hemodynamic indices of early GBS sepsis, rising to greater than two times baseline levels within 11 min of the onset of bacteremia (approximately 1.0 X 10(8) cumulative organisms/kg). In contrast, AOP was unaffected during the first 83 min of GBS sepsis (approximately 25 X 10(8) organisms/kg) but fell from 84 to 47 mmHg in the final 31 min of the experiment. Both CI and MBFI fell monotonically as a function of cumulative GBS dose, reaching 72% and 64% of baseline at 55 min (approximately 12.5 X 10(8) organisms/kg) and 40% and 34% of baseline by 3 hr of sepsis (approximately 125 X 10(8) organisms/kg), respectively. At every GBS dose, the fall in CI was entirely accounted for by a reduction in SVI. SVRI, MVRI, and PVRI were elevated at all times during GBS sepsis. Despite a 34% reduction in systemic oxygen delivery during the first 83 min of GBS infusion (approximately 25 X 10(8) organisms/kg), arterial pH and base excess did not change significantly. Thereafter, pH fell monotonically reflecting the progressive development of metabolic acidosis.

Unsuspected mesenteric hypoperfusion despite apparent hemodynamic recovery in the early phase of septic shock in piglets.

We have developed an animal model of group B beta Streptococcal sepsis especially conducive to observation of hemodynamic sequelae of the early phases of septic shock. In piglets (N = 7), direct continuous measurements were made of aortic pressure (AOP), left atrial pressure (LAP), central venous pressure (CVP), mesenteric artery blood flow (QMES), and pulmonary artery blood flow, equivalent to cardiac output (CO). Systemic vascular resistance (SVR) and regional mesenteric vascular resistance (MVR) were calculated. Sepsis was induced by bolus intravenous administration of live, washed, type 1b group B beta Streptococcus (GBS) at approximately 1 X 10(10) organisms/kg. Early in septic shock, AOP, LAP, CO, and QMES fell to 66%, 20%, 62%, and 34% of pre-GBS levels, respectively, while SVR and MVR rose to 139% and 224% of control. The decrease in QMES and increase in MVR were significantly more extensive than the fall in CO or the rise in SVR, respectively. Subsequently, systemic hemodynamic function improved over time while regional mesenteric circulation did not. AOP and CO recovered to 86% and 88% of pre-GBS levels, respectively, and SVR returned to 105% of baseline. However, QMES remained only 48% of control, and MVR continued at 173% of pre-GBS levels. Mesenteric blood flow could not accurately be inferred from measurements of either AOP or CO during sepsis in these piglets. Relative mesenteric hypoperfusion persisted despite systemic hemodynamic recovery during this GBS sepsis protocol.

Nonhomogeneous redistribution of mesenteric blood flow after tolazoline during group B streptococcal sepsis in piglets.

The effect of tolazoline (Tz) on mesenteric blood flow was evaluated in a piglet model of group B streptococcal (GBS) sepsis. GBS infusion decreased cardiac output and mesenteric blood flow equivalently, while increasing systemic and mesenteric vascular resistance. At three doses between 2 and 25 mg/kg, Tz increased cardiac output and decreased systemic vascular resistance. However, at no dose did Tz improve the diminished mesenteric artery blood flow which accompanied GBS sepsis. The potential use of Tz in neonatal sepsis may be limited by its nonhomogeneous redistribution of blood flow.

Hemodynamic consequences of tolazoline in neonatal group B streptococcal bacteremia: an animal model.

Using a piglet model of neonatal sepsis, we have determined that Group B streptococcal (GBS) bacteremia is associated with a state of vascular hyper-resistance in both the pulmonary and systemic circulations. This elevated vascular resistance is accompanied by a significant fall in cardiac output despite the assurance of constant intravascular fluid volume. Pulmonary artery pressure rises extensively while systemic blood pressure remains essentially unchanged during this GBS infusion protocol. We report here our attempts to relieve the vascular hyperresistance of GBS infusion by administration of an alpha-sympathetic antagonist, tolazoline (Tz). We found that Tz, in a dose-related fashion, decreased both systemic and pulmonary vascular resistance over the entire range from 2 to 25 mg/kg. Further, at all doses tested, the resistance-reducing effect of Tz was equal in the systemic and pulmonary vascular beds. No selective pulmonary or systemic vasodilatory effect was demonstrated by Tz in this model of neonatal pulmonary hypertension. The reduction of systemic vascular resistance was accompanied by a significant elevation in total body cardiac output at all Tz doses. Compared to pre-Tz values, cardiac output rose by 24, 55, and 55% after Tz at 2, 8.3, and 25 mg/kg respectively. In addition, administration of Tz to septic normovolemic piglets reliably produced a transient decrease of systemic blood pressure. For Tz doses of 2 and 8.3 mg/kg, steady state systemic blood pressure returned to pre-Tz levels within 10 min. However, after Tz at 25 mg/kg, steady state systemic blood pressure remained significantly below pre-Tz levels.

Long-term evaluation of pericardial substitutes.

The development of postoperative pericardial adhesions increases the risk of cardiac reoperations because of the danger of damaging the heart, great vessels, or grafts. Several pericardial substitutes have been tested in the past in an attempt to facilitate reoperation, with inconclusive results. This study evaluated eight different materials as pericardial substitutes: six synthetic materials and two different preparations of bovine pericardium. In 32 dogs a 10 by 5 cm piece of pericardium was excised through a right thoracotomy and the defect closed with a measured patch. Each material tested was implanted in four dogs that were put to death at 3, 6, 9, and 12 months. At autopsy the development of adhesions and epicardial reaction were graded as none, minimal, moderate, and severe. Histologic studies of the patch, the epicardium, and the suture line were performed. Our results suggest that both types of bovine pericardium were an excellent substitute. Although minimal adhesions developed, these were easily dissected. The underlying anatomy was clearly recognizable because of the lack of epicardial reaction. Silicone rubber-coated polyester fabric was an acceptable material for the prevention of adhesions, but a severe fibrous epicardial reaction impeded the recognition of the coronary arteries. Both silicone-filled and high-porosity polytetrafluoroethylene (PTFE) films reduced adhesions but caused a severe epicardial reaction. The other synthetic materials were considered inferior because of severe epicardial reaction and/or structural deterioration.