Abstract

Diagnosis and treatment of cardiovascular disease of reptiles and amphibians remain challenging based on lack of normative data, the wide range of adaptive physiologies of these creatures, few case reports, and limited reptile and amphibian specific pharmacokinetic data. Herein I provide an overview of diagnostic and therapeutic approaches for differentiation of reptile and amphibian cardiovascular normality as well as disease and suggestions for treatment.

Introduction

Diagnosis and treatment of cardiovascular disease in reptiles and amphibians remain challenging based on few reported cases, normal baseline data, and fewer successful outcomes.^1-6 Clinical signs may be nonspecific, but those reported will be summarized. Appropriate physical examination and diagnostic approaches will be reviewed as well as cardiovascular treatments. Normal physiological adaptations of the cardiovascular system in reptiles and amphibians, which may obscure diagnosis, will also be highlighted. Therapeutic cardiovascular options will also be summarized. Other than the neoplastic diagnosis of lymphoma, the lymphatic system of reptiles and amphibians appears rarely affected as a primary disease. However, cases of lymphatic disease and expected clinical signs and treatment options will be included.

Cardiovascular and Lymphatic Systems

The cardiovascular and lymphatic systems of reptiles and amphibians will be reviewed in detail by another author; however, for the purposes of this presentation, they will include the heart, veins, arteries, capillaries, and the lymphatic hearts and vessels. These organs serve important roles in delivery of oxygen and other nutrients to organs and cells, maintaining local and systemic fluid homeostasis, and provision of both local and system immune responses. If these organs aren’t working, the body’s ability to maintain immune, respiration, and fluid homeostasis is, to say the least, severely compromised and death may be imminent.

In general, the reptile and amphibian heart is relatively smaller and works much less than that of most endotherms. In addition, reptile and amphibian innate physiologic tolerance of low blood oxygen and low metabolic rate may obscure diagnosis of cardiovascular abnormalities until end-stage disease.¹ Causes of congestive heart failure in reptiles include restrictive cardiomyopathy, cardiac infection, myocardial fibrosis, atherosclerosis, valvular insufficiency, valvular stenosis, and pericardial effusion.⁷ Causes of pericardial effusion in reptiles include infectious pericarditis, noninfectious pericarditis (visceral gout), congestive heart failure, hemopericardium (trauma, aneurysmal rupture, coagulopathy), and neoplasia. Atherosclerosis has been reported in both reptiles and amphibians.

Clinical Signs of Cardiovascular Disease

Often nonspecific in reptiles and amphibians, cardiovascular clinical signs in addition to normal physiological adaptive change vary based on the species and cardiovascular physiology and anatomy, further obscuring the clinical diagnosis (Table 1). Hydration and temperature significantly affect cardiovascular function of both reptiles and amphibians; therefore, the physical examination and diagnostics of the cardiovascular system should be performed while the animal is hydrated and body temperature is within POTZ. For example, in a study of the marine toad (Bufo marinus) and the leopard frog (Rana catesbeiana), both aerobic and cardiovascular capacity were compromised by dehydration, but were less so in the toad.^8,9 Decline in cardiovascular output/blood flow was mainly based on pulse volume but also due to decreased heart rate. Peripheral resistance increased in both species during dehydration, based on hemoconcentration, but was more profound in the frog based on additional peripheral vasoconstriction likely based on the need to maintain hydration.^8,9 Loss of plasma volume was the principal driver of reduced cardiac output in both of these amphibian species. Evaluation of heart rate in reptiles and amphibians is further made a diagnostic challenge based on the ability of the reptile and amphibian heart rate to readily adapt to the environment (Table 2).^9-11 Herptile heart rate is generally lower than that of similarly sized endotherms. Embryonically, species heart rate varies based on species (at the same temperature, lizards and turtles increased compared to snake and crocodilians) and increased temperature. Embryonic heart rates were also relatively increased in species with smaller adults, smaller eggs, and shorter incubation periods. The total number of embryonic heartbeats between oviposition and hatching was relatively decreased in squamates compared to turtles and crocodilia.¹¹ Reptile cardiovascular function is best evaluated at POTZ and may be estimated by the following calculation (although this formula overestimates heart rate in bearded dragons.):²

Reptile heart rate _POTZ: 33.4(Wt_kg^-0.25)

Table 1. Clinical signs of reptiles suffering cardiovascular disease^1-6

Table 2. Causes of physiologic heart rate change in reptiles and amphibians^1,8,9

Select cardiac diagnostic approaches for reptiles and amphibians are provided in Table 3. Many basic approaches easily used for companion mammals are challenging to apply in reptiles. Challenging diagnostics include auscultation, which may or may not be cardiac productive dependent upon the species; ECG, which may have low amplitude and few normal values available; peripheral blood pressure reading, which appears completely unrelated to central vascular pressures; ultrasound based on the small windows and heart of many species; and even CT and MRI, based on the challenge of providing contrast and the small heart size. The author finds the usefulness of ultrasound as a diagnostic highly dependent upon the skill of the operator as well as his or her ability to accept the challenge of reptile cardiac ultrasound.

Table 3. Cardiac diagnostic direction for reptile and amphibians^2,4,12,15,16

Lizards*—Green iguanas, skinks, chameleons, water dragons

Imaging

Heart size may be difficult to measure on radiographs, based on local tissue confluence and lack of cardiac fat.^1,2,6 Ultrasound, CT, or MRI is recommended to best assess cardiac size, although few normal values are yet available. Creation of vertebral heart score for reptile species in which the heart can be radiographically or CT visualized is recommended based on the following vertebrae as baseline:

• Chelonia—Length/width of the last cervical vertebra unattached to the shell.
• Snakes—The 1st vertebra located cranial to the heart, unaffected by boney change as with previous osteomyelitis, within the lung field for ease of measurement.
• Lizards—The first vertebra completely caudal to the scapular wing. Review of a normal animal for comparison imaging is recommended.

Clinical Signs of Lymphatic Disease

Clinical signs of lymphatic disease are poorly documented in reptiles, but are more prominently reported in amphibians.^3,12,13 This dearth of reptile lymphatic disease reports may be based on relative differences in elasticity and permeability of reptile and amphibian skin.¹⁴ In the amphibian, lymph hearts beat synchronously, about once per second, independent of the heart rate.¹⁴ Certainly, in cases of sepsis, shock, hyperthermia or hypothermia, or vasculitis which is widespread, both systems are likely affected. In the amphibian, suspect illness whenever large volumes of lymph accumulate in any lymph sac. For both species, clinical signs may be expected to be like those of humans suffering lymphatic vascular disease, of which the characteristic clinical sign is lymphedema, which should be cytologically and biochemically differentiated from edema or other fluids. Likely because amphibians have an astounding ability to move lymph rapidly in the normal state (fluid leakage from plasma as high as 50 times the total plasma volume over a 24-hour period), because they have so many lymph hearts (15 in the European fire salamander, Salamandra salamandra), and because they have more distensible skin than that of most reptiles, when dysfunction occurs, clinical signs of lymphatic and/or cardiovascular disease in the amphibian may be dramatic and severe.¹³ Hydrops (when large amounts of fluid build up in a newborn animal’s tissues and organs, causing extreme swelling [reserved for tadpoles]) or anasarca (a general swelling of the whole body that can occur when the tissues of the body retain too much fluid, also known as extreme generalized edema) is commonly reported. Peripheral edema alone may also occur. Signs of dermatosepticemia often accompany these signs but may be difficult to detect based on animal coloration and/or the dilution effect of fluid accumulation.

Diagnosis and Treatment of Lymphatic Disease

In humans, lymphatic vascular insufficiency is often genetic in origin, and diagnosis is confirmed via imaging: indirect radionuclide lymphoscintigraphy, magnetic resonance imaging, and CT. In amphibians and reptiles, I suspect lymphatic disease is more often based on serious systemic disease, as seldom is only a single area clinically affected. Differentials should include cardiac disease, infectious disease (viral and bacterial etiologies are most common), and renal or hepatic disease leading to low total protein and/or vasculitis. Prior to treatment of specific lymphatic disease, the clinician is urged to provide adequate supportive care to achieve POTZ, adequate hydration, proper husbandry to include adequate protein/nutritional intake and antibacterial should other signs of sepsis/vasculitis be present. Therefore, diagnostics should include a CBC, biochemistry, and fecal assessment to rule out common whole-body causes of lymphatic disease: parasitism, other organ failure, and bacterial or viral infection.

Treatment of Cardiovascular Disease

A mini formulary for treatment of cardiovascular disease in reptiles and amphibians is provided (Table 4). Unlike in companion mammals, differentials for reptile and amphibian cardiovascular disease are dominated by infectious and acquired (uric acid or mineralization, atherosclerosis) disease. In many cases, cardiovascular disease may not be manageable by cardiovascular drugs or may be better managed by treatment of underlying husbandry insufficiencies or infectious diseases, to include parasitism. Ensure POTZ and adequate hydration and lack of parasitism. In obese animals, create a nutritional plan for weight reduction and/or specific proteins that may reduce signs of atherosclerosis or uricemia and uric acid deposition. Weakness and lack of mobility due to cardiac insufficiency may limit the animal’s ability to obtain food and water, adequate heat, humidity or UVB; rearrangement of the enclosure may be necessary to ensure adequate access. Dietary intake of sodium is usually nonproblematic in reptiles, but overhydration may be problematic in aquatic amphibia; therefore, supplementation with increased sodium and electrolytes either in the enclosure water, drinking or soaking water or food should be considered. Supplementation with fatty acids may be considered, as captive food supplies likely have limited availability of these anti-inflammatory oils compared to free-living counterparts.

Table 4. Cardiovascular drugs for use in reptiles and amphibians^2,5,6,17,18

References

1.  Hynes B, Girling SJ. Cardiovascular and haemopoietic systems. In: BSAVA Manual of Reptiles. BSAVA Library; 2019:323–341.

2.  Kik MJ, Mitchell MA. Reptile cardiology: a review of anatomy and physiology, diagnostic approaches, and clinical disease. In: Seminars in Avian and Exotic Pet Medicine. WB Saunders; 2005;14(1):52–60.

3.  Varshney JP. Diagnosis and management of anasarca in a turtle. Intas Polivet. 2016;17(1):209–210.

4.  Rishniw M, Carmel BP. Atrioventricular valvular insufficiency and congestive heart failure in a carpet python. Australian Veterinary Journal. 1999;77(9):580–583.

5.  Bogan Jr. JE. Ophidian cardiology—a review. Journal of Herpetological Medicine and Surgery. 2017;27(1–2):62–77.

6.  Mitchell MA. Reptile cardiology. Veterinary Clinics of North America: Exotic Animal Practice. 2009;12(1):65–79.

7.  Fitzgerald BC, Dias S, Martorell J. Cardiovascular drugs in avian, small mammal, and reptile medicine. Veterinary Clinics: Exotic Animal Practice. 2018;21(2):399–442.

8.  Hillman SS. Dehydrational effects on cardiovascular and metabolic capacity in two amphibians. Physiological Zoology. 1987;60(5):608–613.

9.  Hillman SS, DeGrauw EA, Hoagland T, Hancock T, Withers P. The role of vascular and interstitial compliance and vascular volume in the regulation of blood volume in two species of anuran. Physiological and Biochemical Zoology. 2010;83(1):55–67.

10.  DeGrauw EA, Hillman SS. General function and endocrine control of the posterior lymph hearts in Bufo marinus and Rana catesbeiana. Physiological and Biochemical Zoology. 2004;77(4):594–600.

11.  Du WG, Ye H, Zhao B, Pizzatto L, Ji X, Shine R. Patterns of interspecific variation in the heart rates of embryonic reptiles. PloS One. 2011;6(12).

12.  Peters JA, Mullen RK. Electrocardiography in Caecilia guntheri (Peters). Physiological Zoology. 1966;39(3):193–201.

13.  Wright KM, Whitaker BR. Amphibian medicine and captive husbandry. Krieger Publishing Company; 2001.

14.  Koltowska K, Betterman KL, Harvey NL, Hogan BM. Getting out and about: the emergence and morphogenesis of the vertebrate lymphatic vasculature. Development. 2013;140(9):1857–1870.

15.  Bhaskar A, Vinod A. Demonstration of the origin of ECG waves. Advances in Physiology Education. 2006;30(3):128.

16.  Paillusseau C, Gandar F, Schilliger L, Chetboul V. Two-dimensional echocardiographic measurements in the ball python (Python regius). Journal of Zoo and Wildlife Medicine. 2020;50(4):976–982.

17.  Williams CJ, Alstrup AK, Bertelsen MF, Jensen HM, Leite CA, Wang T. When local anesthesia becomes universal: pronounced systemic effects of subcutaneous lidocaine in bullfrogs (Lithobates catesbeianus). Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology. 2017;209:41–46.

18.  Mueller CA, Eme J, Tate KB, Crossley DA. Chronic captopril treatment reveals the role of ANG II in cardiovascular function of embryonic American alligators (Alligator mississippiensis). Journal of Comparative Physiology B. 2018;188(4):657–669.