Anadromous fish as biomarkers for the combined impact of marine and freshwater heavy metal pollution.

Rivers along the eastern seaboard of the United States and Canada are becoming increasingly contaminated with heavy metals. This includes the Tusket River (Nova Scotia, Canada) which empties into the Gulf of Maine, near the Bay of Fundy. Whether anadromous fish such as alewife (Alosa pseudoharengus), exposed both to marine and freshwater contaminants, are accumulating these heavy metals and experiencing any changes in their morphology was explored in this study. Adult (4-6 years of age) Tusket River alewife (n = 38) were harvested and had external examinations including morphometrics (fork length, weight). Biopsies were taken and structural abnormalities noted. Morphometric data was compared to historical alewife reference data from 1985. Biopsies of muscle, liver and kidney had heavy metal profiles assessed. Major findings of this study include detectable levels (µg/g wet weight) of a number of heavy metals and concerning maximum concentrations achieved of arsenic (liver: 14 µg/g), cadmium (kidney: 2.6 µg/g), mercury (liver: 0.26 µg/g), magnesium (muscle: 460 µg/g), selenium (kidney: 4.0 µg/g) and zinc (liver: 38.0 µg/g). As well, reduced body weight for length and in 87% of fish, presence of spine curvatures (3-24°) not visible externally were noted. This study is the first detailed report in alewife of key tissue heavy metals, some at levels of concern, reductions in weight for length and spine abnormalities. These findings validate concerns regarding potential impacts of deteriorating conditions of rivers and their surrounding waters such as the Gulf of Maine on anadromous fish species.

Essential and non-essential heavy metal levels in key organs of winter flounder (Pseudopleuronectes americanus) and their potential impact on body condition.

This study explored whether winter flounder, a benthic species, are potentially exposed to contaminants such as heavy metals released from the sediment of the Bay of Fundy/Gulf of Maine, both critical habitats identified to have increases in heavy metal levels. Experimentally in fish, exposure to certain heavy metals resulted in reduced weight for length and structural abnormalities, but it is unknown if this occurs in wild fish. Winter flounder (n = 72), harvested between 2015 and 2018 from the aforementioned western Atlantic region of Canada/USA, had detectable levels of most heavy metals, with some exhibiting levels of concern (arsenic, cadmium, lead, selenium, zinc) in muscle, liver, and kidney. A 1.4% incidence of structural abnormalities was noted. When compared to 1980 regionally matched flounder data, the 2018 flounder had significantly reduced weight for length, exacerbated with age. Clearly winter flounder are affected by worsening heavy metal contaminant levels in this geographic area.

[Validation of the French version of the situational characteristics questionnaire in the measurement of space and motion discomfort]. / Validation de la version française du questionnaire des caractéristiques situationnelles dans la mesure de l'inconfort spatio-moteur.

INTRODUCTION: Space and motion discomfort (SMD) refers to various symptoms that occur in environments with unreliable visual and kinesthetic information that do not permit adequate spatial orientation. Some studies have demonstrated that there is a stable and predictable relationship between vestibular dysfunction and anxiety disorders. Further, vestibular dysfunction can predispose or trigger the development of panic disorder with or without agoraphobia (PD/A) or reinforce phobic avoidance. It therefore seems clinically useful to develop and validate instruments for evaluating SMD in various populations. Measuring SMD could facilitate identification of individuals with PD/A who present comorbid vestibular dysfunction. Jacob et al. developed and validated such a questionnaire: the Situational characteristics questionnaire (SitQ). This questionnaire evaluates the presence of symptoms such as dizziness, vertigo, and instability under specific conditions. The SitQ comprises two subscales that measure SMD and one subscale (agoraphobia) that measures agoraphobic avoidance behaviours. The instrument has two sections. The first section is composed of the SMD-I and agoraphobia subscales, containing 19 and seven items, respectively. Each item consists of two contrasting descriptors of a specific situation or environment. The respondent is required to indicate to what extent the two described situations or environments cause discomfort. Each item includes a "criterion" descriptor for the situation (i.e., a descriptor that is presumed to engender SMD) and an alternative (non-criterion) descriptor. The second section comprises the SMD-II scale; this scale is composed of nine criterion situations, for which non-criterion situations are not supplied. The instrument takes approximately 20 minutes to complete. OBJECTIVE: The present study focuses on the validation of the French-language version of the SitQ: the questionnaire des caractéristiques situationnelles (QCS). METHOD: The sample was composed of French Canadians recruited across Quebec from an anxiety disorders treatment clinic, general psychiatric care clinics, a community organization for individuals with anxiety disorders, advertisements in local newspapers, and ads posted in various public locations. The sample included 141 participants who met the criteria for lifetime PD/A. Participants reported current PD/A (n=73) or PD/A in remission (n=68). The control sample was recruited from undergraduate courses in various disciplines. Two hundred and thirty-five (n=235) students completed the questionnaires. Data from 63 (26.8%) participants were excluded from the analyses due to failure to complete all of the research questionnaires. RESULTS: Analysis of the global descriptive data and the descriptive data for each dependent variable revealed that the data were independent of sociodemographic variables and respected the assumptions of normal distribution (skewness and kurtosis). Parametric tests were subsequently conducted. Using the combined data from the control and clinical groups, the internal consistency of the scales was analyzed using Cronbach's alpha. The SMD-I and SMD-II scales demonstrated good homogeneity. The results were comparable or superior to those obtained with the English-language version of the questionnaire. The agoraphobia scale demonstrated weaker internal consistency and corresponding weaker homogeneity. This result was consistent with that of the original version of the agoraphobia scale; this scale was eliminated for the subsequent analyses. Construct validity was analyzed via t-tests comparing clinical and control groups. Effect sizes were estimated using percentage of variance explained. The SMD-I scale demonstrated weak construct validity and was also eliminated from subsequent analyses. The SMD-II scale demonstrated good construct validity and provided an adequate measure of the theoretical construct of SMD. This scale permitted discrimination of participants according to the presence or absence of PD/A. It is therefore possible to identify participants with PD/A by their level of SMD. This result is comparable to that of Jacob et al. CONCLUSION: The results of the present study are generally consistent with the results of the validation of the original version of the questionnaire. However, the SMD-I and agoraphobia scales in the French-language version of the measure did not achieve a level of significance sufficient to definitively establish validity.

'I'm cured but....': perceptions of illness following treatment.

The current qualitative research studied representations of illness posttreatment from a heart transplant group, a panic disorder group, and a tic disorder group. All three groups were preoccupied with perceptions about the impact of the illness, perception of self and the perception of how others view the ill person. The heart transplant group seem to adopt an active style of coping compared to the panic disorder group who presented a more passive, anticipatory mode of coping, and the tic group who were preoccupied with control over the perceptions of others. This qualitative information could help optimize adaptation strategies.

Hyperoxia causes oxygen free radical-mediated membrane injury and alters myocardial function and hemodynamics in the newborn.

Newborn children can be exposed to high oxygen levels (hyperoxia) for hours to days during their medical and/or surgical management, and they also can have poor myocardial function and hemodynamics. Whether hyperoxia alone can compromise myocardial function and hemodynamics in the newborn and whether this is associated with oxygen free radical release that overwhelms naturally occurring antioxidant enzymes leading to myocardial membrane injury was the focus of this study. Yorkshire piglets were anesthetized with pentobarbital sodium (65 mg/kg), intubated, and ventilated to normoxia. Once normal blood gases were confirmed, animals were randomly allocated to either 5 h of normoxia [arterial Po(2) (Pa(O(2))) = 83 +/- 5 mmHg, n = 4] or hyperoxia (Pa(O(2)) = 422 +/- 33 mmHg, n = 6), and myocardial functional and hemodynamic assessments were made hourly. Left ventricular (LV) biopsies were taken for measurements of antioxidant enzyme activities [superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)] and malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) as an indicator of oxygen free radical-mediated membrane injury. Hyperoxic piglets suffered significant reductions in contractility (P < 0.05), systolic blood pressure (P < 0.03), and mean arterial blood pressure (P < 0.05). Significant increases were seen in heart rate (P < 0.05), whereas a significant 11% (P < 0.05) and 61% (P < 0.001) reduction was seen in LV SOD and GPx activities, respectively, after 5 h of hyperoxia. Finally, MDA and 4-HNE levels were significantly elevated by 45% and 38% (P < 0.001 and P = 0.02), respectively, in piglets exposed to hyperoxia. Thus, in the newborn, hyperoxia triggers oxygen free radical-mediated membrane injury together with an inability of the newborn heart to upregulate its antioxidant enzyme defenses while impairing myocardial function and hemodynamics.

Lower liver transplant success in females: gender differences in metabolic response to global ischemia.

BACKGROUND: Research has shown that gender plays a significant role in the metabolic processes of different organs and that transplanting livers of females into male or female recipients has significantly higher failure rates. To understand why, this study examined whether gender differences exist in various metabolic responses of livers to ischemia. METHODS: The following metabolic liver parameters in Sprague-Dawley rats (male, n = 14; and female, n = 18) were examined; adenosine triphosphate (ATP) and lactate expressed as micromoles/g dry weight, and hydrogen ion content [H+] expressed as 10(-8) mol/L. In vivo liver biopsy specimens were compared with ischemic biopsy specimens at 3, 10, 15, 30, and 45 minutes (37 degrees C). RESULTS: In vivo female ATP values (9.9 +/- 0.8) were similar to males (9.8 +/- 0.9) and both had early, rapid decline during ischemia reaching 20% of baseline by 10 minutes of ischemia. In contrast, male liver lactate accumulation peaked by 3 minutes and at much lower levels (35 +/- 13), whereas female liver lactate peaked by 10 minutes at 71 +/- 11. For the rest of the ischemic period, female livers exhibited significantly (P < .05) greater lactate accumulation. Female liver H+ levels also increased to higher levels (55 +/- 10) than the male livers (37 +/- 7) and this pattern was significantly (P < .05) different from 10 minutes onward. CONCLUSIONS: Although livers of females ultimately have similar ATP profiles to livers of males, they experienced more rapid and greater degree of tissue lactate and H+ accumulation during ischemia. Therefore, female livers have increased acidosis during ischemia, which could adversely affect transplant outcome.

A long-term stable normothermic cardiopulmonary bypass model in neonatal swine.

BACKGROUND: An appropriate animal model of cardiopulmonary bypass (CPB) is critical in order to study the morbidity and mortality in newborn children undergoing long-term cardiac surgery. Since this has been reported to be technically difficult, this paper describes a neonatal porcine CPB model (3 days old, n = 18) for up to 8 h to study long-term bypass. METHODS: After anesthesia, neonates had arterial/venous monitoring lines inserted, they were heparinized (300 IU/kg), the aorta was cannulated for arterial retroperfusion, and a two-stage venous drainage catheter was placed in the right atrium. A Medtronic Minimax Plus oxygenator and the bypass circuit were primed with donor blood and CPB was instituted. RESULTS: Line and mean arterial pressures were kept at 147.7 +/- 73 and 62.7 +/- 9 mm Hg, respectively. Myocardial (38.1 +/- 1.0 degrees C) and rectal temperatures (37.7 +/- 1.0 degrees C) were maintained. Heart rate was 184.8 +/- 34.5 bpm. Hematocrits were 29.6 +/- 6.0%, activated clotting time was sustained above 400 s throughout bypass, blood gas parameters were maintained in the normal range (pH, 7.39 +/- 0.1; PO(2), 123.1 +/- 65.2 mm Hg; PCO(2), 37.2 +/- 8.5 mm Hg; and HCO(3)(-), 21.5 +/- 3.6 mmol/L). CPB was terminated after 8 h and no visceral edema or other imbalances normally associated with swine on bypass were observed. CONCLUSIONS: Results demonstrate a model of stable long-term bypass in neonatal swine which can be used to study issues critical to children requiring surgical correction and CPB at a young age. Overall effects of surgery and bypass on these younger patients have yet to be explored and therefore a stable long-term normothermic model of CPB would allow the study of numerous parameters associated with this complicated procedure.

Is hyperglycemia seen in children during cardiopulmonary bypass a result of hyperoxia?

OBJECTIVE: We sought to identify whether elevated PaO (2) itself can directly cause hyperglycemia in newborns and to document any additional effects of cardiopulmonary bypass on this response. METHODS: Piglets were exposed to either normoxia (88 +/- 6 mm Hg) or hyperoxia (470 +/- 28 mm Hg) in the following studies. Anesthetized 3-day-old neonatal pigs were either ventilated for 2 hours of normoxia (n = 5) or hyperoxia (n = 5) or placed on normothermic, normoxic cardiopulmonary bypass (n = 6) and then randomly assigned to either undergo a 2-hour normoxic period or a 1-hour hyperoxic episode, followed by a return to normoxia for an additional hour. Blood glucose levels were measured in all animals. RESULTS: No significant changes were observed in blood glucose levels in neonatal pigs that underwent 2 hours of normoxic ventilation (5.0 +/- 0.6 mmol/L) or cardiopulmonary bypass (6.6 +/- 1.6 mmol/L). However, the ventilatory model showed a significant and sustained (P <.001) hyperglycemic response after both 1 hour (8.6 +/- 1.0 mmol/L) and 2 hours (9.8 +/- 1.6 mmol/L) of hyperoxia. In the cardiopulmonary bypass model, exposure to 1 hour of hyperoxia elicited a significant (P <.05) hyperglycemic response (10.3 +/- 1.2 mmol/L), followed by a return to normal blood glucose levels (6.6 +/- 1.6 mmol/L) with a return to normoxia. This hyperoxia-mediated hyperglycemic response was confirmed when data examined from children undergoing cardiopulmonary bypass for primary repair of their congenital defects also identified a significant positive correlation (r = 0.72, P =.02) between oxygen levels and blood glucose levels measured before and at the end of cardiopulmonary bypass. CONCLUSIONS: Hyperoxia triggers a hyperglycemic response in both ventilatory and bypass models. Cardiopulmonary bypass does not exacerbate this response, as shown by the similar levels of hyperglycemia sustained for the duration of the hyperoxic exposure in both experimental models. Therefore, not only may hyperoxia play a crucial role in the hyperglycemic response seen during neonatal cardiopulmonary bypass, but its effect on glucose homeostasis should be considered whenever children are exposed to hyperoxia.

Sex hormones and the selective estrogen receptor modulator tamoxifen modulate weekly body weights and food intakes in adolescent and adult rats.

This study documented the effect of changes in male and female sex hormones and the selective estrogen receptor modulator (SERM) tamoxifen on weight gain and food consumption of rats from puberty to adulthood, and assessed whether age at onset of treatment affected outcome. In Study 1, male and female WKY rats were either neutered or sham-operated before puberty, and a subgroup of neutered females underwent estrogen replacement (ERT) at the age of puberty. In Study 2, subgroups of neutered females received either ERT or tamoxifen beginning well into the postpuberty period. Weekly body weight and food consumption were assessed, and food consumption was normalized to metabolic weight (body weight(0.67)). Neutering reduced the rate of weight gain in males (P < 0.05), but significantly increased it in females (P < 0.0001). ERT immediately reduced weight gain and prevented any further increase, resulting in weights below that of sham-operated females (P < 0.05). Tamoxifen prevented further weight gain and returned profiles to that of sham-operated females. Food consumption, normalized to metabolic weight, was similar in females and males, and both sexes showed a decrease through maturation to adulthood. Neutering decreased food consumption below that of sham-operated animals in both males and females (P < 0.05), and ERT returned it to sham levels. Despite the fact that tamoxifen had an effect on body weight similar to that of ERT, females receiving tamoxifen treatment consumed less food than both sham-operated and ERT females (P < 0.05). Weight gain is modulated by sex hormones in male and female rats, with both estrogen and tamoxifen exerting immediate effects in females, irrespective of the age at which treatment is initiated. Differences in food consumption do not appear to account for the effects of hormones and tamoxifen on body weight, suggesting that they exert a direct effect on overall body metabolism.

Gender-differences in myocardial adaptation to afterload in normotensive and hypertensive rats.

Echocardiographic studies suggest that women appear to exhibit a greater degree of myocardial hypertrophy in response to increased afterload than men. Therefore, gender differences and the role of estrogen and testosterone in the development of myocardial hypertrophy were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Male and female rats were either surgically neutered or underwent a sham operation at 21 days of age. A subgroup of neutered females of each strain received 17beta-estradiol replacement. At 6 months, the heart weight-to-body weight ratio was assessed and correlated with systemic blood pressure. Compared with males, females had significantly smaller body and heart weights in both normotensive and hypertensive strains. Despite this, females consistently had significantly greater heart weight-to-body weight ratios. In females, neutering significantly lowered the heart weight-to-body weight ratio in WKY rats, which was returned to intact levels with estrogen replacement. Female SHR showed similar, but not statistically significant, responses. In males, neutering appeared to result in a higher heart weight-to-body weight ratio in WKY rats, but the opposite was seen in SHR. In addition, there was a significant correlation between arterial blood pressure and heart weight-to-body weight ratio (systolic r=0.45, P=0.0015: diastolic r=0.52, P=0.0002) in intact males and females of both strains, and for a given diastolic pressure, females always exhibited a greater heart weight-to-body weight ratio than males. Thus, a greater degree of myocardial hypertrophy in females appears to be related to the presence of estrogen in both normotensive and hypertensive rats. Females show a stronger relationship between heart/body weight and blood pressure than males, which occurred independent of the presence of estrogen.

Metabolic and functional response of neonatal pig hearts to the development of ischemic contracture: is recovery possible?

The potential for functional and metabolic recovery in neonatal hearts after the development of ischemic contracture remains controversial and undefined. This study documents post-ischemic recovery of metabolism and function in the in vivo neonatal heart after the development of onset and peak ischemic contracture. In piglets on cardiopulmonary bypass, hearts were reperfused after the development of either onset (TICo) or peak (TICp) ischemic contracture. Systolic (developed and systolic function, contractility) and diastolic (diastolic function, relaxation) performance was assessed throughout reperfusion. Biopsies were obtained at end-ischemia or end-reperfusion to assess metabolism. By end-ischemia, the metabolic profiles of both TICo and TICp hearts confirmed energy-store depletion and purine degradation that was quantitatively greater in TICp hearts. Hearts reperfused at TICo had consistent moderate impairment of developed function, contractility, diastolic function, and relaxation, whereas hearts reperfused at TICp had much more profound functional impairment. Diastolic function showed the worst functional recovery. In contrast, systolic function was not significantly altered in either study group and, thus, did not reflect the actual extent of injury. In addition, TICo hearts either did not further deplete or partially regenerated energy stores during reperfusion, whereas TICp hearts had further energy-store depletion and lactate accumulation. In summary, neonatal hearts reperfused after TICo maintained or partially restored energy stores and had significant but incomplete functional recovery. In contrast, further metabolic deterioration and profound functional impairment occurred with reperfusion after TICp, potentially indicating ongoing mitochondrial injury and compromised oxidative phosphorylation.

Does the degree of cyanosis affect myocardial adenosine triphosphate levels and function in children undergoing surgical procedures for congenital heart disease?

OBJECTIVE: The outcome of children with cyanosis after cardiac surgical procedures is inferior to that of children who are acyanotic. Animal studies indicated detrimental effects of chronic hypoxia on myocardial metabolism and function. We studied whether the presence or the degree of cyanosis adversely affected myocardial adenosine triphosphate, ventricular function, and clinical outcome in children. METHODS: Forty-eight children who underwent repair of tetralogy of Fallot were divided according to their preoperative saturation: group I, 90% to 100% (n = 14 patients); group II, 80% to 89% (n = 16 patients); and group III, 65% to 79% (n = 18 patients). Adenosine triphosphate was measured from right ventricular biopsy specimens taken before ischemia, at 15 minutes of ischemia, at end-ischemia, and at 15 minutes of reperfusion. Ejection fraction was measured by echocardiography. RESULTS: Even before surgical ischemia, compared with groups I and II, group III had lower preoperative ejection fraction (59% +/- 2.9% vs 67% +/- 1.7% and 68% +/- 1.0%; P <.01) and lower preischemic adenosine triphosphate levels (15.1 +/- 2.1 vs 19.1 +/- 1.9 and 21.4 +/- 1.5 micromol/g dry weight; P <.01). After 15 minutes of ischemia, group III had lower adenosine triphosphate levels (11.2 +/- 1.8 vs 14.77 +/- 2.3 and 17. 6 +/- 3.1 micromol/g dry weight; P <.01). With reperfusion, both cyanotic groups lost further adenosine triphosphate compared with partial recovery in the acyanotic group (-22% +/- 3.8%, -20% +/- 3. 1% vs +18% +/- 1.8%; P <.01). Children in group III had a more complicated postoperative course as evidenced by longer ventilatory support (85 +/- 25 hours vs 31 +/- 15 and 40 +/- 21 hours; P =.07), inotropic support (86 +/- 23 hours vs 38 +/- 12 and 36 +/- 4 hours; P <.01), and intensive care unit stay (160 +/- 35 hours vs 60 +/- 10 and 82 +/- 18 hours; P =.02). CONCLUSIONS: The degree of cyanosis adversely affects myocardial adenosine triphosphate, function, and clinical outcome of children who undergo cardiac operation. Children with cyanosis should be identified as a higher risk group that could be targeted for supportive interventions.

Extracellular calcium concentration affects susceptibility to global ischemic injury in newborn but not adult hearts.

BACKGROUND: Whether immaturity in calcium handling, that persists for a time after birth, could increase sensitivity to extracellular calcium and affect the development of global ischemic injury in the newborn heart is unknown. To address this, the impact of alterations in extracellular calcium concentration on newborn vs. adult development of myocardial injury due to ischemia was studied. METHODS: In Study 1, hearts of 3-day-old piglets and adult pigs were perfused with 1 of 3 different calcium concentrations: control (0.13 mmol/L); intermediate (2.23 mmol/L); high (4.44 mmol/L) before normothermic ischemia. In Study 2, newborn hearts were allocated to perfusion with or without the L-calcium channel antagonist verapamil before high (4.44 mmol/L) calcium exposure, followed by normothermic ischemia. Tolerance to ischemia was assessed by determining the time to irreversible injury in all hearts, and maximal intraventricular pressures at peak injury. RESULTS: In adults, altering calcium did not significantly affect tolerance to ischemia. In newborns, increasing calcium exposure resulted in significantly greater intraventricular pressures at maximal injury when compared with the control (low) calcium group (p<.05). As well, newborns exposed to high calcium had a significantly shorter time to the development of ischemic injury compared with the other groups (p<.05). Those newborn hearts pretreated with an L-calcium channel antagonist before the high calcium exposure did not exhibit this increased susceptibility to ischemic injury (p<.05). CONCLUSIONS: In contrast to adults, the development of ischemic injury in the newborn heart is affected by changes in extracellular calcium, that can be modified with an L-calcium channel antagonist. This information could be used to prolong the safe preservation time of newborn donor hearts harvested for transplantation, as well as to minimize postoperative ventricular dysfunction.

Multiple in vivo full-thickness myocardial biopsies by freeze-clamping.

A technique was developed to permit multiple large biopsies of the in vivo myocardium to measure certain metabolites (ATP, CP, myocardial glycogen, lactate) with minimal chance of ventricular fibrillation or severe alterations in the heart's ability to maintain BP. Adult pigs with normal hearts (n = 9) as well as with hypertrophy (n = 5) created by aortic banding 3-4 months prior were anesthetized, intubated, and ventilated. After a sternotomy, the pericardium was opened and the epicardial surface was cleared of any adhesions. Biopsies were taken from the distal to proximal end of the heart. A suture (3-O Prolene) was placed in a figure-eight pattern in the area to be biopsied. A piece of the myocardium (50-100 mg) was grasped using a pair of narrow dressing forceps and frozen in liquid nitrogen. When the sample was completely frozen, a No. 11 scalpel blade, held at a 90 degrees angle to the epicardium throughout the cut, was used to carve out the full thickness biopsy. The sample was placed immediately in liquid nitrogen. The myocardial defect was repaired by using the previously placed suture buttressed with pieces of subcutaneous fat to prevent tearing the epicardial surface. This in vivo biopsy method has negligible complications and can be repeated or taught with constant reliability.

Surgical model of volume overload-induced ventricular myocardial hypertrophy (VHvo) to study a clinical problem in humans.

Cardiac patients with aortic or mitral valve incompetence often suffer from VHvo and are at higher risk of surgery compared to other patients undergoing heart surgery. Hypertrophied hearts are known to have altered metabolism and function. Therefore, it is imperative to use hearts with similar pathology as found in clinical patients when studying ways to better protect them. We herein report a model of VHvo developed in our laboratory. Pigs (n = 10) weighing 21 kg were anesthetized, intubated, and mechanically ventilated in dorsal recumbency. Bilateral femoral arterio-venous side-to-side anastomoses were created at least twice the diameter of the vessels. Patency was confirmed and the animals grew to maturity with this pathology, at which time they were sacrificed. Severe hypertrophy was documented with significantly greater heart weight to body weight ratio, LV free wall thickness, and septum. This surgical model of VHvo is associated with minimal complications and no pericardial adhesions. This allows for accurate metabolic and functional heart studies to be conducted at a later date.