Abstract

Since 1982, the California Marine Mammal Center (CMMC) has investigated morbidity and mortality in harbor seal neonates. Prematurity is a frequent observation (36.4%) and all pups with lanugo coats (63.6%) exhibit patent ductus arteriosus (PDA).

Pulmonary disease is the most prominent cause of morbidity and mortality in the harbor seal pups seen at CMMC. Clinical respiratory distress associated with pulmonary congestion and edema may be attributable to some defect in the left side of the heart with blood shunting from left to right through a PDA.

Eight neonatal harbor seals were examined clinically via radiography, electrocardiography, arterial angiography, and arterial blood gases in an attempt to detect the presence of PDA in the live animal.

The occurrence of ductal patency in an animal such as a seal, with the multiple circulatory adaptations to diving and stress, may he physiologic and adaptive as opposed to pathologic and detrimental to the animal. Prematurity accompanied by embarassment, resulting in lowered oxygen tension and occurrence Of pulmonary edema/ combine to have a detrimental effect on harbor seal pup survivability.

Introduction

Phoca vitulina richardsi, the Pacific harbor seal, lives in waters along the Pacific coast from northwest Mexico to Alaska, where mixed male and female herds inhabit rocky, sandy, or muddy shares and inlets. In northern California where the California Marine Mammal Center (CMMC) is located, harbor seal pupping season is mid-March to early June.

Pups are typically born with spotted adult pelage; the creamy-white lanugo coat having been shed in utero. The mature harbor seal pup is precocious, born on land but due to tidal fluctuation, swimming and diving within hours of birth. Pups classified as premature are those born early in the pupping season, retaining the lanugo coat, measuring 6-10 cm smaller in standard length (standard length = 86 cm) (1), 5-10 pounds lighter in weight (standard weight = 24 lbs) (2), and possessing an anatomic patent ductus arteriosus (PDA) at necropsy.

Materials and Methods

Eight beached or abandoned harbor seal pups rescued from the northern California coast were admitted to the CMMC during the inonths of March and April, 1982-1984. At admission, each animal was given a complete physical examination. Age was estimated by examining umbilical stump characteristics as listed in Table 1 (3.4).

Table 1. Age Estimation by Umbilivcal Stump Characteristics

Complete blood counts (CBC's) and chemistries were done on blood samples collected from the extradural vein of each animal. Thoracic radiographs were taken on eight harbor seal pups, both in lateral and dorso-ventral views. Electrocardiography was done an all eight pups. Each animal was positioned in sternal recumbency and the leads attached as in Figure 1.

Figure 1.

If excessive animal movement produced EKG artifacts, the animal was given 1-2 mg Valium (Roche, Nutley, NJ) intravenously.

Umbilical artery catheterization was performed on five of the harbor seal pups; those in which the umbilicus was fresh enough to allow surgical cut-down to the "triad" of two umbilical arteries and one umbilical vein. A 3-1/2 french polyethylene arterial line was then passed to the approximated level of the aortic arch and 6 cc of Renografin-76 (Squibb, Princeton, NJ) was instilled into the circulation.

Arterial blood gas analysis was done on samples of four harbor seal pup bloods drawn sequentially from the umbilical arterial line.

Necropsies were performed on all animals that died during hospitalization.

Results

Seven out of eight pups were admitted early in the pupping season and retained lanugo coats. All pups, except one, weighed less than 17 pounds. The eighth pup had a weight of 19 pounds, 11 ounces and had a spotted coat. This animal was the only one considered mature.

Packed cell volume, hemoglobin values, and red blood cell numbers were all within normal range (5,6). The pups that did not survive tended to have lower white cell counts (< 7,000/mm ) associated with a neutrophilia and lymphopenia. Overall, serum globulin levels were decreased (< 2.2 g/dI) (5). Hyperbilirubinemia existed in all pups; the younger the pup, the higher the bitirubin value (7).

Clinically, on examination of the cardiovascular and respiratory systems, no bounding pulses were noted, but two out of eight pups, both with lanugo coats, exhibited a systolic murmur with a gallop rhythm. Initially there were no, or only mild, signs of respiratory distress and tachycardia, but these signs progressed to apnea, bradycardia, and the presence of auscultable harsh or moist rales Terminal signs were those of severe pulmonary edema and rapid labored biphasic respirations associated with an expiratory grunt.

Initial thoracic radiographs exhibited slight to moderate cardiomegaly, increased pulmonary vascularity, and biventricular enlargement, but progressed to pulmonary edema where the cardiac silhouette was actually obscured.

One of the electrocardiograms (that of the only spotted pup) was within normal limits. The other seven EKG's were suggestive of PDA (8). increased amplitude and duration of "P" waves, sometimes notched; and tall "T" waves suggestive of volume overload (see Figure 2) (9).

Of the five harbor seal pups with angiograms, two had PDA's that were functionally closed (one of these being the full-term spotted pup). A third (premature) pup had a slight left to right shunt of contrasted material through its PDA. A fourth pup had a moderate left to right shunt and the fifth pup had a large enough flow, left to right, that the cardiac catheter actually flowed directly through the PDA shunt.

Arterial blood gas analysis of the latter three premature pups revealed trends of decreased oxygenation associated with hypercarbia over a 15 to 60 minute period. In one animal (the term pup again), arterial oxygenation increased and hypercarbia decreased.

Necropsies revealed pulmonary edema grossly in all the harbor seals characterized as premature. The single mature (spotted) pup had purulent congested lungs on necropsy.

Discussion

Clinically on cardiovascular and respiratory system examination in the human neonate with PDA, there can be bounding peripheral pulses, systolic murmur with possibly a gallop rhythm, mild signs of respiratory distress associated with tachycardia progressing to periods of apnea, and bradycardia with auscultable crepitant rales. The occurence of congestive heart failure in severe cases leads to rapid labored biphasic respirations with expiratory grunts (8).

Pulmonary edema--the abnormal accumulation of interstitial fluid in the lung to the extent that it becomes clinically significant--is a prominent cause of morbidity and mortality in premature harbor seals (4, 10). The pathologic processes that could be leading to pulmonary edema in our premature harbor seal are: 1) lung immaturity, 2) immune deficiency, 3) PDA/CHF, 4) pneumonia, 5) drowning, and 6) overheating.

Controlled studies of immune status and lung maturity are now being formulated.

Bacterial and viral lung cultures are necessary to rule out pneumonia. Overheating and drowning are less likely differential possibilities, since admission examination temperatures were within the normal range (37-38 C) and the animals' coats were dry.

PDA certainly is contributing to pulmonary edema in that too much blood is being returned to the heart to the point where the heart is unable to pump all of it into the systemic circulation, leading to a subsequent increase in pulmonary vascular pressure.

Although the EKG cannot diagnose the severity of PDA, it can and does suggest the presence of such an entity.

Theoretically in utero, the fetal right ventricle pumps blood to the systemic circulation bypassing the lungs, via the ductus arteriosus (right to left shunt). At birth, there normally is a functional closure of the ductus involving contraction of vascular smooth muscle in the ductal wall. Increased oxygen tension when the animal takes its first breath causes the release of Prostaglandin E, mediating ductal closure, in human neonates (11). So once the animal breathes, blood flow is no longer right to left through the ductus, but right to lung. If the ductus remains patent--which can in human neonates be caused by stress, respiratory distress, or pulmonary edema (lowered oxygen tension so no closure signal goes to the ductus)--or if the musculoelastic tissue of the ductus is defective due to prematurity, there may arise a left to right shunt through the ductus arteriosus as is seen in three of our harbor seals.

Decreased arterial blood oxygenation and increasing hypercarbia, over time, in these three pups suggests the ductus is actually "stealing" arterial blood from the aorta and abdominal organs. The single (fourth) animal, that had increasing oxygenation and decreasing hypercarbia, had a functionally closed ductus arteriosus on angiography. This full-term pup presumably died for reasons other than PDA or pulmonary edema. The animal's white cell count was 5,000 and purulent material found in the lungs is suggestive of pneumonia. Histopathology is not yet completed.

Deaths in harbor seal pups with symptomatic PDA's are generally related to respiratory distress and prematurity. With good oxygen ventilation, a fairly high birth weight, and normal white blood cell counts, we might expect pups to survive. The following treatment protocols are therefore being investigated in an attempt to increase survivability of the harbor seal pups; A) the use of natural surfactant transtracheally to hasten lung tissue maturity, B) the use of hypergammaglobulin to stimulate immune system development, C) medical management including restriction of fluids, diuretics, bronchodilators, antibiotics, digitalization, vasocilators, positive pressure oxygen ventilation (IPPV) (5) (in infants without IPPV, PDA leads to increasing dyspnea, increasing oxygen requirement, and apneic periods) (12), and D) the use of indomethacin, a chemical inhibitor of prostaglandin used successfully in some human neonates in association with IPPV oxygen (13).

The use of indomethacin to assist in ductal closure may be uncalled for in our harbor seal pups. In full-term harbor seal, crabeater, monk seal pups (as well as cetacean neonates), and all precocious swimmers and divers in the wild, Slijper (14) found delayed ductal anatomic closure, suggesting that during diving--when lowered oxygen tension exists--the ductus may remain open to accomodate the hypoxic state the pup finds itself in. Slijper found that the ice seat pups, who remained on land instead of entering the water, had earlier anatomic closure of their PDA's. This may suggest that a patent ductus arteriosus in a healthy full-term harbor seal with mature pulmonary vasculature may have an adaptive, as opposed to a detrimental, effect.

In the pre-term harbor seal where there is respiratory embarrassment resulting in lowered oxygen tension accompanied by pulmonary edema, the left to right shunt may indeed play a detrimental role in the animal's subsequent death.

In school children who live at high altitudes (low oxygen tension), the incidence of PDA is 1/150 children, as opposed to 1/4,000 children in the general sea level school children population (11).

Acknowledgements

The authors would like to thank Dr. Linda Lowenstine ,Dept. of Vet. Pathology University of California, Davis; Dr. Ronald Clyman, University of California, School of Medicine, San Francisco; and Dr. Ron Cohen, Mount Zion Hospital, San Francisco for their help in this preliminary project.

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