Pathophysiology of Heart Failure in Broiler Chickens: Structural, Biochemical, and Molecular Characteristics1

Pathophysiology of Heart Failure in Broiler Chickens: Structural, Biochemical, and Molecular Characteristics1 A. A. Olkowski2 Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, S7N 5A8, Canada underlying molecular and biochemical changes in the cardiomyocytes, contractile apparatus, and extracellular matrix in the ventricular myocardium are critically evaluated and discussed with reference to the clinical signs associated with deterioration of heart pump function. The secondary pathophysiological effects on the cardiovascular system, resulting from hemodynamic changes associated with the failing heart pump, are also reviewed and critically discussed.

Key words: broiler, heart failure, ascites, sudden death syndrome, hypoxemia 2007 Poultry Science 86:999–1005

broiler flocks. Frequently, apparently normal broilers in very good body condition die suddenly without any discernible preexisting clinical signs. However, the birds that succumb to SDS frequently have a history of cardiac rhythm disturbances, and individuals showing severe ventricular arrhythmia are at high risk of sudden death. There are sex differences in the incidence of arrhythmia with frequency in males being higher than in females, and the prevalence of SDS is considerably higher in male broilers (Olkowski and Classen, 1998a). The etiology of SDS is associated with ventricular arrhythmias, and catastrophic ventricular fibrillation is the cause of cardiac death (Olkowski and Classen, 1997). Cardiac rhythm disturbances are common among fastgrowing broilers (Greenlees et al., 1989; Grashorn, 1994; Olkowski et al., 1997; Olkowski and Classen, 1998a; Korte et al., 1999). The incidence of arrhythmia in the fast-growing broiler population can be as high as 27% (Olkowski and Classen, 1998a). Broilers subjected to a dietary restriction regimen are less susceptible to cardiac rhythm disturbance, and when broilers are maintained on a ration equivalent to approximately 60% ad libitum, the incidence of arrhythmia may be reduced to less than 2%. This indicates that broilers selected for rapid growth are predisposed to cardiac rhythm disturbances, and the risk of cardiac arrhythmia is directly associated with rapid growth because even moderate control of growth rate by dietary restriction considerably decreases the incidence of arrhythmia. The incidence of cardiac arrhythmia in slow-growing chicken breeds, such as Leghorns, is usually less than 1%.

INTRODUCTION In comparison with other classes of chickens, broilers are highly susceptible to heart failure. Ascites syndrome and sudden death syndrome (SDS) are the most common heart-related conditions in modern broiler flocks (Olkowski and Classen, 1998a; Korte et al., 1999). Electrocardiographic data and necropsy findings (Olkowski et al., 1997, 1998) obtained from cross-sectional studies of otherwise normal flocks indicate that a relatively large number of fast-growing broilers shows evidence of subclinical heart disease and may be at risk for acute or chronic heart failure. This is likely associated with the genetic selection of broilers for growth and feed conversion efficiency, while neglecting basic physiological requirements (Scheele, 1997). Acute heart failure (SDS) and chronic heart failure (hypoxemia, ascites) are the leading noninfectious causes of mortality and morbidity in modern broiler flocks.

ACUTE HEART FAILURE Acute cardiac death (SDS) accounts for majority (Olkowski and Classen, 1998a) of mortalities in commercial

©2007 Poultry Science Association Inc. Received October 31, 2006. Accepted November 19, 2006. 1 Presented as part of the Metabolic and Cardiovascular Disease Symposium, July 19, 2006, at the Poultry Science Association Meeting, Edmonton, Alberta, Canada. 2 Corresponding author: [email protected]

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ABSTRACT Modern strains of fast-growing meat type poultry are highly susceptible to heart failure. Heart-related mortalities are observed predominantly in fastgrowing broiler chickens, with ascites and sudden death syndrome being the most common heart-related conditions in modern broiler flocks. This paper examines the role of structural, molecular, and biochemical factors pertinent to the pathophysiology of heart failure in fastgrowing broilers. Evidence explaining the pathogenesis of acute and chronic heart failure, in the context of the

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Figure 1. Electrocardiogram of a broiler chicken challenged with stress factor adrenaline. Note a very severe arrhythmogenic response to the simulated stress.

All arrhythmias may carry a potential risk. The more complex the arrhythmic episodes are, the greater the risk, but in some circumstances even a mild arrhythmic episode could degenerate to a catastrophic event. Given the high predisposition of broilers to arrhythmia and high incidence of SDS, losses associated with acute heart failure in broilers are of economical significance. The pathogenesis of cardiac disrhythmias in broiler chickens is still poorly understood. More basic research is required to understand the causes underlying arrhythmogenesis to develop strategies for control of SDS in fast-growing broilers.

CHRONIC HEART FAILURE In clinical terms, chronic heart condition in broilers may be manifested as several distinctive clinical entities. In mild cases, hypoxemia is the prevailing sign of heart pump insufficiency, whereas in more advanced cases, congestion in pulmonary circulation can also be found on necropsy examination. In many broilers, progression of chronic heart failure results in the accumulation of fluids in body cavities with pericardial effusion and ascites being the most prominent signs. Clinical and necropsy data indicate that many fastgrowing broilers may be at risk for chronic heart failure. The evidence presented here was compiled from laboratory experiments and field studies and includes clinical observation, postmortem findings, electrocardiography, echocardiography, and hemodynamic measurements. Gross Pathology and Histopathology. Necropsy findings obtained from cross-sectional studies involving large populations of otherwise normal broiler flocks indicate that a relatively large number of fast-growing broilers show evidence of subclinical heart disease (Olkowski et al., 1997, 1998). Characteristic gross pathological changes seen in broilers consist of left and right ventricular and atrial dilation. In the affected hearts, the ventricular muscle wall was thin and lacked the tone of healthy heart muscle. Degeneration of the left atrio-ventricular valve apparatus was also a common finding (Olkowski et al., 1998). These changes were particularly prominent in the hearts from ascitic broilers.

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Cardiac arrhythmias in broiler chickens may occur as early as 7 d of age, and the incidence increases with age. Ventricular arrhythmias (VA) are the most prevalent disturbances of the rhythm, with the most common being premature ventricular contractions. The pathophysiological effect of heart rhythm disturbances may vary depending on type of arrhythmia, its complexity, and duration of arrhythmic episode. For example, episodic premature ventricular contractions may be of little clinical significance, whereas complex and sustained ventricular arrhythmias may present a high risk of acute heart failure and sudden cardiac death. Premature ventricular contractions in birds have been associated with electrolyte imbalance including hypokalemia or hypomagnesemia, thiamine or vitamin E deficiency, and several viral diseases (Lumeij and Ritchie, 1994). Although arrhythmias associated with outright vitamin or mineral deficiencies are rather unlikely to occur in modern broiler flocks, the risk of arrhythmia and SDS may be increased when some nutrients are supplemented in excess (Nain et al, 2006). Ventricular arrhythmias may be caused by factors such as stress, coronary artery disease, heart ischemia or infarction, cardiomyopathy, pericardial disease, hypoxemia, hypercapnia, and idiopathic causes. In some instances occurrence of arrhythmia and SDS in broilers can be explained by lesions in the pericardium and mural myocardium (Kawada et al., 1994; Olkowski et al., 2003), but in many cases the pathogenesis of cardiac disrhythmias in broiler chickens is poorly understood. Undoubtedly, rapid growth provides an environment conducive to the expression of arrhythmogenic factors. Hypercapnia (elevated blood pCO2) and hypoxemia (lowered blood pO2) are common features in many fast-growing broilers (Olkowski et al., 1999, 2005a). In this context, of interest is the apparent arrhythmogenic effect of hypercapnia in broilers (Korte et al., 1999). Stress may trigger complex arrhythmia in susceptible broilers, and in many cases sudden death may occur immediately following some stressful event (A. A. Olkowski, S. Nain, C. M. Wojnarowicz, B. Laarveld, and J. Alcorn, Univ. Saskatchewan, unpublished data). An example of stress induced cardiac arrhythmias is shown in Figure 1.

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Figure 2. Serial recordings of heart rate in Leghorn chickens, feedrestricted slow-growing broilers (broiler R), fast-growing broilers fed ad libitum (broiler A-L), and broilers with fulminant heart failure and ascites. Onset of ascites (indicated by circle) occurred mainly during the fifth week.

fractional shortening. The Doppler study shows that left atrio-ventricular valve insufficiency is also a common feature, and ascitic chickens have a history of valve apparatus malfunction. The changes observed on echocardiographic examination are prominent features seen at the onset of clinical signs in all ascitic birds. Moreover, our studies demonstrated that broilers that eventually developed ascites show impaired heart function long before the onset of clinical signs of ascites (Olkowski et al., 2005a). Cardiac Performance, Blood Flow, and Blood Gas Parameters. Landmarks of deteriorating heart function in broilers include high incidence of cardiac arrhythmia (Olkowski and Classen, 1998a) and progressive deterioration of heart pump function associated with progressive bradycardia (Olkowski and Classen, 1998b). Figure 2 shows changes in heart rate at various stages of growth in growing Leghorn chickens (resistant to ascites) slowgrowing broilers (low incidence of heart failure and ascites), fast-growing broilers fed ad libitum (high incidence of heart failure and ascites), and broilers with fulminant heart failure and ascites. It is noteworthy that, in comparison to slow-growing chickens, heart rate in fast-growing broilers is considerably lower throughout the growth period. Notably, in birds that developed ascites, there was a significant progressive decline in heart rate long before the onset of clinical signs. Heart rate decreases at the onset of ascites has also been observed by others (Kirby et al., 1997; Roush et al., 1997; Wideman et al., 2000). Direct measurements of cardiac output and in vivo evaluation of fractional shortening (Olkowski et al., 1999, 2005a,b) showed that heart performance and consequently blood flow in fastgrowing broilers and ascitic broilers is considerably impaired. Poor performance of the heart is a major factor involved in the pathogenesis of hypoxemia in fast-growing broilers. Several large cross-sectional studies in our lab (Olkowski et al., 1999, 2005a) have shown that in comparison to slow-growing broilers or leghorns, fast-growing broilers

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Lesions in the pericardium are common in broilers succumbing to heart failure and ascites. Typical lesions involving pericardium in fast-growing broiler chickens are characterized by excessive pericardial effusion, focal adhesions between parietal and visceral components of the pericardium with fibrous deposits on visceral pericardium, and thickened pericardium. Echocardiographic evidence indicates that severe pericardial effusion, adhesions, or both may have a restrictive effect on heart pump function, where diastolic and systolic function of the heart may be affected (Olkowski et al., 2003). Ultrastructural and Molecular Changes. Electron microscope examination of diseased hearts revealed that the architecture of cardiac extracellular matrix and sarcomeres is severely disturbed. The fine network of collagen struts was disrupted, and the mesh of endomysial collagen encompassing cardiomyocytes was considerably reduced in the affected hearts. The most extensive changes in the extracellular matrix were observed in the myocardium from ascitic birds. A significant reduction in the myofibril component occurs in hearts from ascitic broilers. Together with changes in the collagen matrix, these features explain the characteristic thin and flaccid appearance of ventricular muscle, commonly seen upon postmortem examination of hearts from ascitic birds and some apparently normal birds (Olkowski et al., 2001). Degeneration of proteins responsible for contraction of heart muscle in ascitic birds may account for poor performance of the left ventricle, which is clinically evidenced by impaired ventricular wall motion, reduced fractional shortening, and reduced cardiac performance (Olkowski et al., 1999, 2005a). Changes in Heart Function Observed on Electrocardiographic and Echocardiographic Examination. Electrocardiographic measurements showed that, in comparison to slow-growing broilers, fast-growing broilers had significantly lower heart rate. It is remarkable that ascitic birds show a history of a characteristic precipitous declining heart rate pattern (Olkowski and Classen, 1998b). In birds with advanced ascites, the decline in HR was in the range of 40 to 60% of the values observed in nonascitic birds of the same age. In some broilers developing ascites, a markedly decreased heart rate is clearly noticeable in the second week of life, i.e., some 10 to 14 d before the clinical signs of ascites develop. The fact that the pattern of declining heart rate in fast-growing broilers is seen long before the appearance of any obvious clinical signs suggests that subclinical heart condition is involved in the pathogenesis of ascites. Particularly compelling evidence regarding chronic heart failure was derived from echocardiographic evaluation of heart function (Olkowski et al., 2003, 2005a). Because this technique is not invasive, it allows repeated examination of the same individuals in vivo, and the progression of the heart failure can be followed. In our studies, the echocardiographic examination clearly demonstrates that many fast-growing broilers show early depression of the left ventriculum function, which is evidenced by impaired ventricular wall motion and reduced

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OLKOWSKI Table 1. Arterial and mixed venous blood pO2 and pCO2 values, in Leghorn chickens, feed-restricted slowgrowing broilers, ad libitum fed fast-growing broilers, and broilers with ascites

Leghorns Slow-growing broilers Fast-growing broilers Broilers with ascites

pO2 mmHg (arterial blood)

pO2 mmHg (central venous blood)

pCO2 mmHg (arterial blood)

pCO2 (central venous blood)

85.76 77.9 58.9 34.1

42.88 42.9 28.8 17.5

19.94 27.5 35.84 53.3

23.82 40.62 44.8 59.4

associated with overall low cardiac energy reserve, and in particular, inadequacy of reserve and low levels of important energy substrates (high-energy phosphate). It is of interest to consider the changes in heart function observed in fast-growing broilers in our studies in the context of disturbances in the thyroid status of broilers susceptible to ascites (Scheele et al., 1992; Decuypere et al., 1994; Gonzales et al., 1999; Buys et al., 1999, Luger et al., 2001, 2002). It is noteworthy that characteristic cardiovascular changes associated with hypothyroidism include low heart rate and decreased cardiac output and pericardial effusion (Sylvia Vela and Crawford, 1995; Guyton and Hall, 1996). Thyroid hormone regulates the contractile properties of the heart as well as the expression of the alpha and beta heavy chains of myosin (Canavan et al., 1994). Physiological levels of thyroid hormones may be an important modulator of the normal maturation of the beta-adrenergic system in the developing ventricular myocardium (Novotny et al., 1999). Taken together, disturbances in thyroid hormones and insufficiency of energy metabolism in the cardiac muscle may represent a metabolic bottleneck in fast-growing broilers. Several key changes in heart function such as depressed heart rate, impaired ventricular wall motion, reduced fractional shortening, and ultimately, lowered cardiac output observed in our studies are consistent with these metabolic insufficiencies. Studies to further elucidate metabolic factors involved in poor performance of the heart in fast-growing broilers are currently underway in our lab. Pathophysiology of Chronic Heart Failure and Ascites. No doubt, evolution of ascites in broilers is associated with pulmonary hypertension, and our findings confirmed that pulmonary hypertension is an important etiological factor in the pathogenesis of right ventricular failure and ascites in broilers raised at low altitude. However, our data also brought up several new facts explaining pressure buildup in pulmonary circulation. It has been suggested that pathogenesis of pulmonary hypertension is associated with a vascular bed unable to accommodate increased cardiac output (for review see Wideman, 2001). In our studies, however, histopathological examination of lung tissue revealed that lungs of normal fast-growing hypoxemic broilers, as well as ascitic broilers, are generally underperfused (Olkowski et al., 2005b). This is consistent with lowered cardiac output and blood flow (Olkowski et al., 1999, 2005a).

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have lowered blood pO2 and elevated blood pCO2. Our overall findings on blood gas data in chickens are summarized in Table 1. Blood oxygenation status depends on the interaction of 3 basic factors: ventilation, diffusion, and perfusion (blood flow). It has been suggested that high blood flow rate in the pulmonary vasculature limits blood oxygenation (for review see Wideman, 2001). However, our in vivo study (A. A. Olkowski, T. Duke, and C. M. Wojnarowicz, Univ. Saskatchewan, unpublished data), in which we used echocardiography to examine broilers at different stages of growth, showed that blood velocity in pulmonary inflow is approximately 25% lower in hypoxemic and preascitic broilers in comparison with normal broilers. Fedde et al. (1998) showed that neither ventilation nor diffusion limitations appear to be factors of practical significance in the predisposition of fast-growing broilers to hypoxemia. This is in complete agreement with our findings (Olkowski et al., 2005b). So, if increased blood flow, ventilation, and diffusion are insignificant as factors affecting blood oxygenation, the possible causes of hypoxemia seen in apparently normal fast-growing birds should be considered in the context of a) inadequate perfusion or b) increased oxygen utilization. Indeed, inadequate lung perfusion, inability to raise cardiac output in the face of oxygen demand, and increased oxygen utilization are the key etiological components of hypoxemia in fast-growing broilers (Olkowski et al., 1999, 2005b). Blood gas measurements showed that a large subpopulation of commercial broilers shows evidence of pathologically changed levels of blood gas parameters. Hypercapnia (elevated blood pCO2) and hypoxemia (lowered blood pO2) are common features in many fast-growing broilers (Olkowski et al., 1999, 2005a). As much as 20 to 30% of apparently normal birds show lowered partial pressure of oxygen in the arterial blood or central venous blood consistent with the state of hypoxemia. All ascitic broilers show profound hypoxemia, but there is a poor correlation between hypoxemia and the risk of ascites. Many fastgrowing broilers are profoundly hypoxemic but not ascitic. This indicates that hypoxemia is not a critical factor in the pathogenesis of ascites but rather is a sign associated with heart failure. Metabolic Studies. Our most recent studies (A. A. Olkowski, S. Nain, C. M. Wojnarowicz, B. Laarveld, and J. Alcorn, Univ. Saskatchewan, unpublished data) pointed out that the deterioration of the heart function may be

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capnia seen in broilers could cause a clinically significant increase in pulmonary arterial pressure (Olkowski et al., 2005a). Hence, increased blood CO2 in broilers must be taken into consideration as a factor causing pulmonary hypertension. Critical Evaluation of Current Evidence on Pathogenesis of Ascites. Substantial work advancing the knowledge on the pathogenesis of hypoxemia and ascites has been performed by studying pathophysiological, metabolic, and molecular features in normal and diseased chickens. Our data and the findings of others discussed above provide evidence that primary causes of hypoxemia and pulmonary hypertension are associated with a chronic pathological process in the left heart. On the other hand, over the years our findings have been questioned based on a tenet that the inability to meet high oxygen demand to support rapid growth, subsequent lack of oxygen, and ensuing hypoxemia and increased cardiac output are the key factors causing pulmonary hypertension in broilers (for review see Julian, 1993, 2000; Wideman, 2001). Interestingly, however, a critical evaluation of our work (Olkowski et al., 1999, 2003, 2005a,b) and the work of others (for review see Wideman, 2001) revealed that the problem is not with the findings per se (which are in essence similar to ours), but rather there are major differences in the interpretation of the data, with the main point of contention being blood flow dynamics. In view of similarities of data, and yet such opposing hypotheses on the basic etiology of pulmonary hypertension, it is important to critically discuss the differences in the interpretation of the results. Wideman et al. (2000) reported the following mean morphometric and blood flow data a) for normal broilers, BW 2,375 g; total ventricular weight 10.4 g, right ventricle weight 2.4 g, left ventricle weight 7.97 g, stroke volume 1.41 mL, and cardiac output values of 471 mL/min, and b) for preascitic birds, BW 2,780 g; total ventricular weight 10.5 g, right ventricle weight 2.91 g, left ventricle weight 7.57 g, stroke volume 1.60 mL, and cardiac output of 520 mL/min. Indeed, right ventricle mass and cardiac output appear to be higher in preascitic birds, but it is important to note that these birds were considerably larger (BW 2,789 g) than normal birds (BW 2,375 g), and naturally, larger birds would have proportionally larger hearts and higher cardiac output. However, a critical evaluation of the data set from the study of Wideman et al. (2000) reveals that their findings are consistent with our findings and in essence confirm our original observations (Olkowski et al., 1999). This becomes obvious if one considers the confounding effect of differences in BW between normal and preascitic birds in the study of Wideman et al. (2000). The reasoning for this is as follows: Because cardiac output changes markedly with body size, for meaningful comparative purposes this variable must be adjusted to account for different body size (Guyton and Hall, 1996). In this context, reinterpretation of the morphometric and blood flow data from the work of Wideman et al. (2000), while accounting for differences in BW between the preas-

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There are several pieces of evidence that must be carefully considered when deliberating the etiology of pulmonary hypertension and ascites. Postmortem examination of hearts in ascitic broilers clearly indicates dilation of the left ventricle and left atrium. Changes in the geometry of the left atrium and left ventricle result from chronically increased hemodynamic burden in the left side of the heart. Consequently it must be taken into consideration that left-sided heart failure must play a significant primary role in the pathogenesis of ascites because such pathological changes cannot be secondary to right ventricular failure. Many fast-growing broilers show evidence of dilated cardiomyopathy, and some eventually develop ascites (Olkowski et al., 1998, 1999, 2001; Wu et al., 2003). Research evidence discussed above points out that progression of pathological process in the myocardium is the primary cause of impaired heart function in fast-growing broilers. Rationale How Failure of the Left Ventricle Contributes to Pulmonary Hypertension. Left ventricular failure can cause increased pressure in pulmonary circulation by passive and reactive mechanisms. In chronic situations, abnormal performance of the left ventricle, atrium, or both will result in a buildup of pressure in the pulmonary arteries (Marshall and Marshall, 1997). Recently, increased pulmonary vascular resistance has been shown to be associated with chronic left ventricular failure as a result of structural remodeling in pulmonary arteries and changes in vascular smooth muscle tone (Driss et al., 2000; Moraes et al., 2000). Increased left atrial pressure may directly induce pulmonary artery constriction (HermoWeiler et al., 1998). Changes in Blood Gas Parameters in the Context of Pulmonary Hypertension. The assumption that pulmonary hypertension can be triggered by hypoxemia in broilers raised at low altitude is physiologically not tenable. Hypoxemia is not the determinant of hypoxic pulmonary vasoconstriction (Duke and Killick, 1951). In normal atmosphere, hypoxemia will not result in pulmonary hypertension, even when mixed venous pO2 is reduced to 10 Torr (Marshall and Marshall, 1983). Low atmospheric oxygen may trigger pulmonary vasoconstriction, but this can happen only when oxygen levels are below 60 Torr, which is unrealistic under normal situations. Further, it should be noted that all hypoxemic broilers also have elevated levels of blood CO2, and if one remains mindful of the metabolic interrelationship between blood pO2 and pCO2, it would become obvious that hypoxemia in broilers cannot be a result of lack of oxygen. In the recent study (Olkowski et al., 2005a), we pointed out that elevated blood pCO2 in broilers may be of significance in the etiology of pulmonary hypertension in broilers. There is a substantial body of older and recent research evidence that chronic hypercapnia is a factor mediating pulmonary hypertension (Kilburn et al., 1969; Rothe et al., 1985; McGuire and Bradford, 2001; Balanos et al., 2002, 2003). Hypercapnia is a prominent feature present in all hypoxaemic birds, and the levels of hyper-

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Table 2. Relevant morphometric and hemodynamic data combined from Tables 1 and 3 (Wideman et al., 2000), expressed as indices of BW

Normal Preascitic

Total V (%BW)

Right V (%BW)

Left V (%BW)

Cardiac index (mL/min/kg of BW)

0.438 0.378

0.101 0.105

0.336 0.272

198.32 187.05

Stroke volume (mL/kg of BW) 0.5936 0.5754

ACKNOWLEDGMENTS While presenting this research material, the author gratefully recognizes the contribution of H. L. Classen. The research presented in this paper has been supported by grants provided by the Poultry Industry Council and NSERC.

Balanos, G. M., K. L. Dorrington, and P. A. Robbins. 2002. Desferrioxamine elevates pulmonary vascular resistance in humans: Potential for involvement of HIF-1. J. Appl. Physiol. 92:2501–2507. Balanos, G. M., N. P. Talbot, K. L. Dorrington, and P. A. Robbins. 2003. Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography. J. Appl. Physiol. 94:1543–1551. Buys, N., C. W. Scheele, C. Kwakernaak, and E. Decuypere. 1999. Performance and physiological variables in broiler chicken lines differing in susceptibility to the ascites syndrome: 2. Effect of ambient temperature on partial efficiencies of protein and fat retention and plasma hormone concentrations. Br. Poult. Sci. 40:140–144. Canavan, J. P., J. Holt, and D. F. Goldspink. 1994. The influence of thyroid hormones on the growth of the atria and ventricles of the heart in immature rats. J. Endocrinol. 142:171–179. Decuypere, E., C. Vega, T. Bartha, J. Buyse, J. Zoons, and G. A. Albers. 1994. Increased sensitivity to triiodothyronine (T3) of broiler lines with a high susceptibility for ascites. Br. Poult. Sci. 35:287–297. Driss, A. B., C. Devaux, D. Henrion, M. Duriez, C. Thuillez, B. I. Levy, and J. B. Michel. 2000. Haemodynamic stresses induce endothelial dysfunction and remodeling of pulmonary artery in experimental compensated heart failure. Circulation 101:2764–2770. Duke, H. N., and E. M. Killick. 1951. The effect of anoxia on the pulmonary arterial pressure. J. Physiol. 114:3–4. Fedde, M. R., G. E. Weigle, and R. F. Wideman. 1998. Influence of feed deprivation on ventilation and gas exchange in broilers. Relationships to pulmonary hypertension syndrome. Poult. Sci. 77:1704–1710. Gonzales, E., J. Buyse, J. R. Sartori, M. M. Loddi, and E. Decuypere-E. 1999. Metabolic disturbances in male broilers of different strains. 2. Relationship between the thyroid and somatotropic axes with growth rate and mortality. Poult. Sci. 78:516–521. Grashorn, M. 1994. Investigation of the aetiology and pathology of sudden death syndrome in meat-type chickens. Archiv Fur Geflugelkunde. 58:243–244. Greenlees, K. J., O. Eyre, J. C. Lee, and T. C. Larsen. 1989. Effect of age and growth rate on myocardial irritability in broiler chickens (42861). Proc. Soc. Exp. Biol. Med. 190:282–285. Guyton, A. C., and J. E. Hall. 1996. Textbook of Medical Physiology. 9th ed. W. B. Saunders, Philadelphia, PA. Hermo-Weiler, C. I., T. Koizumi, R. Parker, and J. H. Newman. 1998. Pulmonary vasoconstriction induced by mitral valve obstruction in sheep. J. Appl. Physiol. 85:1655–1660. Julian, R. J. 1993. Ascites in poultry. Avian Pathol. 22:419–454. Julian, R. J. 2000. Physiological, management and environmental triggers of ascites syndrome: A review. Avian Pathol. 29:519–527. Kawada, M., R. Hirosawa, T. Yanai, T. Masegi, and K. Ueda. 1994. Cardiac lesions in broilers which died without clinical signs. Avian Pathol. 23:503–511. Kilburn, K. H., T. Asmundsson, R. C. Britt, and R. Cardon. 1969. Effects of breathing 10% carbon dioxide on the pulmonary circulation of human subjects. Circulation 39:639–653. Kirby, Y. K., R. W. McNew, J. D. Kirby, and R. F. Wideman, Jr. 1997. Evaluation of logistic versus linear regression models for predicting pulmonary hypertension syndrome (ascites) using cold exposure or pulmonary artery clamp models in broilers. Poult. Sci. 76:392–399. Korte, S. M., A. Sgoifo, W. Ruesink, C. Kwakernaak, S. van Voorst, C. W. Scheele, and H. L. Blokhuis. 1999. High carbon dioxide tension (PCO2) and the incidence of cardiac arrhythmias in rapidly growing broiler chickens. Vet. Rec. 145:40–43. Luger, D., D. Shinder, V. Rzepakovsky, M. Rusal, and S. Yahav. 2001. Association between weight gain, blood parameters,

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citic and normal birds, clearly demonstrates that blood flow is actually lower in preascitic birds in comparison with normal birds (Table 2). The conclusion from the reinterpreted data set of Wideman et al. (2000) is that values for stroke volume and cardiac output relative to BW are lower in preascitic broilers, which essentially confirms our observations that blood flow decreases during the development of ascites (Olkowski et al., 1999, 2005a). Further, it is noteworthy that, when heart ventricles mass is corrected for the differences in BW between preascitic and normal broilers, there is very little difference in right ventricle mass, but rather the left ventricle is considerably smaller in preascitic birds. This is also consistent with our findings (Olkowski et al., 1999) and the findings of Martinez-Lemus et al. (1998). It is important to note that findings from echocardiography (MartinezLemus et al., 1998) and morphometry (Olkowski et al., 1999) showed that in comparison to slow-growing chickens (low risk of ascites), fast-growing broilers (high risk of heart failure and ascites) have smaller structural and functional hearts, and more specifically, a reduced capacity of the left ventricle. Interestingly, is has been argued that the elevated ratio between right ventricle weight and total ventricular weight ratio provides evidence that right ventricular hypertrophy is caused by pulmonary hypertension (for review see Julian, 1993, 2000). However, it is important to point out that when the morphometric data of the heart are properly corrected for the differences in BW (see Table 2), it becomes clear that the ratio appears higher indeed, but this is not because the right ventricle is larger but rather because the left ventricle is smaller. This of course further puts into question the validity of the argument that higher right ventricle weight to total ventricular weight ratio is an early sign of right ventricle hypertrophy in the pathogenesis of ascites (Wideman, 2001). In conclusion, our findings indicate that chronic heart pump failure is a major factor in the pathogenesis of hypoxemia, pulmonary hypertension, and ascites. As argued above, this contention has been fully collaborated by the study of others.

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METABOLIC DISEASE SYMPOSIUM

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