Size concerns regarding pig hearts for xenotransplantation

Estimation of organ size is essential in xenotransplantation, and body weight (BW, kg) is generally used as an index for size matching. However, direct BW pairing between species can be deceptive, particularly when animals differ markedly in full mature size, such as domestic boars (350 kg) vs. male baboons (30 kg). It is not surprising to learn that a pig heart may be nearly twice the size of that of a baboon with an equal BW, such as 10 kg, since younger animals have organs that are proportionally larger in relation to their total body mass. Moreover, organ maturity is also an important consideration. A 10-kg domestic pig is considered very juvenile since, in nature, domesticated sows usually nurse their litters for 8 to 12 weeks, and piglets reach weights exceeding 15 kg. Forced early weaning when piglets weigh 5 to 8 kg is frequent in modern intensive production husbandry.Nevertheless, organs from 10-kg piglets are considered physiologically immature, and their ability to grow in a well-accommodated xenoenvironment within amature or growing recipient remains uncertain. The limited references available are sufficient to relate the heart sizes of pigs and monkeys based on adjustedBW.Current understanding of heart size variation in domestic pigs during growth stages can also be used to prognosticate the size change of a xenotransplanted pig heart. Heart weight (HW, g) varies close to the first (0.98) power of BWover essentially thewholemammalian range. The exponent of best fitting, HW5 6.0 BW, regressed from data of 104 species, has 95% confidence limits of 70.02, and is independent of sex or habitat (terrestrial vs. aquatic) [1]. In practice, the HWmakes up the same fraction of BW for most mammals, with the European wild boar at a mature size of 90 kg providing a perfect example of this fraction, namely 0.6% [2]. The stated value varies within a specified range. For example, dogs have an HW/BW ratio of 1.0% (HW5 1.0BW), while adult primates (from less than 10-g tree shrews to over 100-kg gorillas, including 70-kg humans) exhibit a ratio of 0.5% (HW5 5.1BW) [3], representing a relatively small HW compared with other mammals. Domestic pigs, direct descendents of wild boars, have an exceptionally lowHW compared with their ancestors or other mammals. Early surveys showed that the HW/BW ratio decreases with increasing BW, reaching only about 0.29% around adolescence (90 kg), with the proportion being even less at full maturity [4]. The great reduction in HW, as an anatomical and physiological adaptation to domestication and extensive husbandry, remains obscure in its origin. However, recent intensive husbandry, which has been characterized by selection for higher leanness (vasculature) and better growth performance (larger mature size), has resulted in concurrent increases in visceral weights, including those of the heart, lung, spleen, liver, and kidney, with the HW ratio reaching 0.34 to 0.39% in 90-kg Yorkshire pigs [5]. The consequence of selection for growth performance in HW of domestic pigs was further proven by a different study that also demonstrated that the vascular space (blood/plasma volume) is no better than fractional BW as a basis for expressing HW in pigs [6]. In contemporary domestic pigs at different stages of maturity, a regression of HW5 12.2 BW with r5 0.96 was identified [6]. The exponent was similar to the exponent of metabolic size, the fractional expression preferred being 0.734 [7] or 0.75 [8]. Since the metabolic size also remains a satisfactory first approximation for comparing growth rates and energy exchanges during growth [9], a constant relationship between heart size and metabolism or energy turnover may exist during the growth of pigs [6]. This relationship also exists for different forms of pigs, and possibly also in other mammals. The HW/BW exponents of the European wild boar (HW5 17.5 BW, calculated from [2]), domestic pigs of almost a half-century ago (HW5 9.7 BW) [4], and domestic miniature pigs on offshore islands in South-East Asia (HW5 9.8 BW, unpublished data) are all very metabolic size-related to current domestic pigs. Apparently, the heart grows only concurrently with metabolism or energy turnover in all different kinds of pigs, although the basal level (regression coefficient) may differ, namely while the regressions may not be equal, they are parallel. Notably, in monkeys of different ages, the sizing exponent of HW5 5.7 BW [7] is also related to energy turnover, just as in pigs, as 0.69 essentially equals metabolic size. Therefore, there is little reason to believe that a pig heart will grow beyond its metabolic range even when xenotransplanted into a baboon, provided it can be well accommodated and/or sized into the energy flow of the new environment. Xenotransplantation 2006: 13: 12–13 Printed in Singapore. All rights reserved doi: 10.1111/j.1399-3089.2005.00269.x Copyright r Blackwell Munksgaard 2006