The guinea pig as an animal model for studying perinatal changes in microvascular function

Abstract

INTRODUCTION: Microvascular dysfunction, characterized by inappropriate vasodilatation and high blood flow in the peripheral microcirculation, is linked to physiologic instability and poor outcome in neonates. specifically, preterm neonates have significantly higher levels of baseline microvascular blood flow than term neonates at 24 h postnatal age. Because of similarities between human and guinea pig endocrine profiles and maturity at birth, we hypothesized that preterm guinea pig neonates would provide a suitable model for studying the mechanisms underlying transitional microvascular function. RESULTS: Guinea pigs that were delivered preterm showed immaturity and had markedly reduced viability. Baseline microvascular blood flow was significantly higher in preterm animals than in term animals. No effect of intrauterine growth restriction or birth weight on baseline microvascular blood flow was observed in either preterm or term animals. DISCUSSION: These results are consistent with recent clinical findings and support the use of the guinea pig as a suitable model for future studies of the mechanisms underlying perinatal microvascular behavior. METHODS: Guinea pigs were delivered either prematurely or at term. Laser Doppler flowmetry was used to study microvascular blood flow at 23 h postnatal age. In term infants, the circulation undergoes rapid and extensive changes in the initial hours of extrauterine life to allow the infant to effectively deal with extrauterine systemic vascular resistance and hence provide normal and adequate perfusion of tissues (1-3). The transitional circulation of preterm neonates (especially those born at ≤30 wk gestation) differs significantly from infants born at full term. In the preterm infant, several crucial physiologic responses to extrauterine life are commonly delayed, allowing for persistence of atrial and ductal shunting and inappropriate blood flow throughout the periphery during the perinatal period (4)(5)(6)(7)(8).Previous studies in preterm infants suggest that abnormal microvascular tone, characterized by inappropriate vasodilatation of the peripheral microvasculature, may contribute to the development of circulatory compromise (4,8). These studies found that the functional integrity of the microvasculature (including appropriate control of vasodilatation) in preterm neonates is significantly altered as compared with neonates born at later gestational ages (GAs). Very preterm neonates (born at 24-28 wk GA) are known to have significantly higher microvascular blood flow at 24 h postnatal age than preterm neonates born at 29-34 wk GA and neonates born at term. High baseline microvascular blood flow in premature infants is significantly correlated with clinical illness severity and poor outcome in the immediate postnatal period (4,9). Such dysfunction in the microvasculature is also a well-established observation associated with the onset of other causes of multisystem organ failure in neonates (10).In addition to disorders relating to short gestation, intrauterine growt...

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“…Nevertheless we believe that our study provides strong clinical data that this pathway is involved in microvascular tone regulation during circulatory transition. Furthermore, it highlights both the need for mechanistic studies utilising available animal models [13], [53], and alternative measures of H 2 S production. Exhaled H 2 S may provide us with better temporal resolution of H 2 S production [54].…”

Microvascular circulatory dysregulation driven in part by cystathionine gamma‐lyase: A new paradigm for cardiovascular compromise in the preterm newborn

“…Preterm animals were delivered by non‐recovery caesarean section at 62 ± 1 days gestational age (GA; full term in this cohort is 71 days). We have previously determined that neonates delivered at this gestational age are equivalent to a human neonate of approximately 29 weeks of gestation and display similar changes in microvascular function to the preterm human …”

“…Term animals were delivered by non‐recovery caesarean section at GA69 or earlier if the pubic symphysis had been fully open for two consecutive days. Delivery was performed as previously described . Briefly, pregnant dams were administered atropine (atropine sulfate, 0.05 mg/kg; Apex Laboratories, Somersby, Australia) prior to surgery and anesthetized by inhalation of 4% isoflurane (Attane; Bomac, Hornsby, Australia).…”

“…Excess fluid in the lungs, nose, and throat was removed by suction. Preterm animals were administered surfactant (100 μL Poractant Alfa, Curosurf; Douglas Pharmaceuticals, Auckland, New Zealand) via the oropharynx as previously described . All pups received a minimum three minutes of continuous positive air pressure respiratory support in 50% oxygen.…”

“…Pups were fed two hourly using a commercial guinea pig milk replacement formula (Wombaroo Food Products, Glen Osmond, Australia), immediately following laser Doppler assessment of cutaneous microcirculatory flow. Neonatal well‐being was scored at feeding times using a model‐specific neonatal monitoring score based on three criteria—respiration (graded from 0 [no breathing] through to 4 [normal, regular breaths]), posture (graded from 0 [profound hypotonia] through to 4 [no spasticity, freely mobile]), and behavior (graded from 0 [none] through to 4 [active and alert]), with higher scores reflecting greater physiological stability …”