Author + information
- Received September 20, 1995
- Revision received August 5, 1996
- Accepted September 9, 1996
- Published online December 1, 1996.
- V. Mohan Reddy, MD⁎,
- John R. Liddicoat, MD,
- Doff B. Mcelhinney, MS,
- Jeffrey R. Fineman, MD,
- Judith R. Klein, MD,
- Roger Chang and
- Frank L. Hanley, MD
- ↵⁎Address for correspondence: Dr. V. Mohan Reddy, 505 Parnassus Avenue, M593, San Francisco, California 94143–0118.
Objectives A reproducible fetal animal model of single-ventricle physiology was created to examine the effects of pharmacologic agents commonly used in the perinatal and perioperative intensive care management of patients with a single ventricle.
Background Single-ventricle physiology is characterized by parallel pulmonary and systemic circulations, with effective blood flow to each determined by the relative resistances in the pulmonary and systemic vascular beds. Perinatal and perioperative management of these patients is largely based on empiric observations and differs considerably between institutions and is further complicated by the transitional physiology of the newborn. The lack of animal models of single-ventricle physiology has hindered the understanding of this problem.
Methods A 10-mm, Damus-Kaye-Stansel-type aortopulmonary anastomosis was created in 10 fetal sheep at 140 ± 1.2 days of gestation. The main pulmonary artery was ligated distally, and pulmonary blood flow (Qp) was provided through a 5-mm aortopulmonary shunt. Eight lambs were delivered at term and placed on cardiopulmonary bypass (30 min) 48 to 72 h after birth. Pharmacologic interventions (0.1 Mg/kg body weight per min of epinephrine, 2 mEq/kg of sodium bicarbonate and 10 mg/kg of calcium chloride) were performed before and after bypass, and hemodynamic responses were observed. The response to the epinephrine bolus was determined only in the postbypass study.
Results Both before and after bypass, epinephrine infusion and calcium and bicarbonate administration increased Qp and systemic blood flow (Qs) (total cardiac output) but produced only small changes in the Qp/Qs ratio (-0.5% to -7.3% change). With the epinephrine bolus, Qp increased enormously, and the Qp/Qs ratio increased by 584% (p < 0.001).
Conclusions In neonatal lambs with single-ventricle physiology created in utero, epinephrine infusion and calcium and bicarbonate administration increased total cardiac output without significantly compromising the Qp/Qs ratio. However, epinephrine bolus seems to be hemodynamically detrimental in circumstances of single-ventricle physiology and should be used with caution and probably in relatively lower doses in the resuscitation of patients with single-ventricle physiology. Further investigation of the dose-dependent effects and the effects of prolonged administration of common pharmacologic agents will enable better management of patients with single-ventricle physiology.
* This study was presented at the 44th Scientific Session of the American College of Cardiology, New Orleans, Louisiana, March 1995. It was supported in part by Grant RO1-HL43357 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.
- Received September 20, 1995.
- Revision received August 5, 1996.
- Accepted September 9, 1996.
- American College of Cardiology