Effect of development on coronary vasodilator reserve in the isolated guinea pig heart.

Toma, B.; Wangler, Roger D.; Dewitt, Donald F.; Sparks, Harvey V.

doi:10.1161/01.res.57.4.538

Cited by 38 publications

(18 citation statements)

References 30 publications

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“…The present findings concerning the effect of maturation of rabbits on maximal coronary flow rates are similar to previous findings of Toma et al (17) in guinea pigs. These investigators found that postnatal growth and maturation were associated with a decrease in maximal coronary flow rate per unit cardiac mass during pharmacologic vasodilation of isolated hearts with adenosine and nitroprusside.…”

Section: Maximal Coronaryjlow Rates Several Factors May Have Con-supporting

confidence: 93%

“…The differences in maximal flow rates in this study parallel changes in myocardial capillarity that have previously been demonstrated in immature and mature animals (17) and in response to long-term exposure of maturing rodents to hypoxia (1-3). Thus, it would seem most likely that they occurred as a consequence of differences in myocardial microvascular density and relative cross-sectional area of the myocardial microvascular bed (i.e.…”

Section: Maximal Coronaryjlow Rates Several Factors May Have Con-supporting

confidence: 85%

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Effect of Growth and Maturation in a Hypoxic Environment on Maximum Coronary Flow Rates of Isolated Rabbit Hearts

Holmes

Epstein

1993

Pediatr Res

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ABSTRACT. This study was designed to determine the effect of growth and maturation of rabbits in a hypoxic (H) environment on the ability to perfuse myocardium. Rabbits were raised in either a normoxic (N) (Po2 = 19.7 kPa or 149 torr) or an H environment (Po2 = 8.6 kPa or 65 + 3 mm Hg) and were studied at ages 5 wk (immature) and 12 wk (mature). Coronary flow (CF) was measured at baseline, during infusion of a maximally dilating concentration of adenosine (A), and at peak reactive hyperemic response to transient inflow occlusion in an isolated, non-blood-perfused heart preparation. Hearts were unloaded, paced at a constant rate (200 beatslmin), and perfused at a constant inflow pressure (50 mm Hg). Regional CF was measured, using microspheres, in right ventricular, left ventricular, and atrial cardiac segments during vasodilation with A. H rabbits developed right ventricular but not left ventricular segment hypertrophy/hyperplasia. CF was greater in immature than mature hearts and higher in H than N hearts during baseline, vasodilation with A, and at peak reactive hyperemia (two-way analysis of variance, p 5 0.05). Regional CF during vasodilation with A was greater in immature than mature hearts, in both right and left ventricular segments, and higher in H than N hearts in all cardiac segments (two-way analysis of variance, p 5 0.05). Differences in total and regional CF between H and N hearts were present at both study ages (t test, p 5 0.05). The differences in CF at baseline show that, under conditions of reduced Oz availability (bloodless perfusate), myocardial perfusion was better in immature than mature hearts and was improved by growth in hypoxia. On the other hand, the differences in CF during infusion of A and at peak reactive hyperemia show that the maximum capacity for myocardial perfusion was also better in the immature hearts and further improved by growth in hypoxia, even in segments undergoing hypertrophy/hyperplasia. These findings suggest an important adaptation to environmental hypoxia in growing, maturing rabbits: an increased intrinsic vascular capacity to perfuse hypertrophied and nonhypertrophied myocardium. Supported by an American Heart Association-Florida Affiliate Clinician Scientist Award (CS89/1) (G.H.). 5Acclimation of immature rodents to environmental hypoxia is associated with development of increased capillary density and capillary to myofiber ratios in both hypertrophied right and nonhypertrophied left ventricular myocardium (1-3). As a result of these increases in myocardial vascularity, intramyocardial diffusion distance for O2 is believed to be reduced, and ability to oxygenate myocardium is thought to be improved to some extent (2, 3). There is, however, a current paucity of data regarding the potential consequences of hypoxia-related changes in myocardial vascularity on myocardial perfusion.Turek et al. (4) studied the effect of raising rats at simulated altitude of 3500 m (hypobaric hypoxia) on regional coronary flow responses to ventilation with a gas mixture containing 1 ...

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Section: Maximal Coronaryjlow Rates Several Factors May Have Con-supporting

confidence: 93%

Section: Maximal Coronaryjlow Rates Several Factors May Have Con-supporting

confidence: 85%

Effect of Growth and Maturation in a Hypoxic Environment on Maximum Coronary Flow Rates of Isolated Rabbit Hearts

Holmes

Epstein

1993

Pediatr Res

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“…Although this area of research has received comparatively little attention, one study has concluded that coronary flow in isolated, 1-week-old guinea-pig hearts is as, or more, sensitive to exogenous adenosine as adult hearts (18). This appears consistent with a report that supported the importance of adenosine in the regulation of coronary flow in the newborn lamb (10).…”

Section: Introductionsupporting

confidence: 65%

Maturation of coronary responsiveness to exogenous adenosine in the rabbit

1987

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Previous studies have indicated that some cardiac control systems, such as autonomic innervation, are incomplete in the newborn and undergo postnatal maturation. However, relatively little is known of maturational changes which will affect the ability of the coronary circulation to regulate blood flow during various interventions. We tested the hypothesis that the coronary circulation of the rabbit develops a progressive, age related increase in responsiveness to exogenous adenosine during the first 16 weeks of life. We examined the response of coronary circulation to exogenous adenosine in four age groups (6-10 days, 3-4 weeks, 7-8 weeks, 16 weeks) of rabbits by using an isolated heart preparation. Coronary flow was measured during an control period, during reactive hyperemia (following release of a 2 min coronary flow interruption), and during infusions of exogenous adenosine. All age groups had similar levels of control coronary blood flow, with a large increase in flow observed during reactive hyperemia. The volume of coronary flow was higher during reactive hyperemia (P less than 0.001) in the 6-10-day-old animals than in the other age groups. However, the 6-10-day-old age group showed a smaller (P less than 0.01) flow response to exogenous adenosine than the other age groups. In addition, the 6-10-day-old animals required higher adenosine concentrations to produce an initial detectable coronary flow increase and to produce the maximal flow response. Additional studies demonstrated a significant reduction in percentage flow debt repayment after theophylline administration in adult rabbit hearts. However, neonatal rabbit hearts showed no change in flow debt repayment following theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…- 32 Gain values of coronary autoregulation in sham-operated control rats in our study were slightly smaller than the values in in situ working hearts 1 - 33 or isolated, blood-perfused, empty beating hearts 1 of larger animals such as dogs. At present, however, no data concerning the pressureflow relation in blood-perfused hearts of small animals are available to compare with our data.…”

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confidence: 58%

Normalization of impaired coronary circulation in hypertrophied rat hearts.

1990

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We tested the hypothesis that impaired coronary autoregulation, decreased flow reserve, and diminished reactive hyperemic response in hypertrophied hearts with coronary arterial hypertension may be reversible after relief of pressure overload. In 4-week ascending aortic banded rats, in vivo peak systolic left ventricular pressure increased to 178±8 mm Hg (103±6 mm Hg in sham-operated control group). This increased pressure produced myocardial hypertrophy, and the left ventricular weight/body weight ratio was 46% above that of the control group. After the rats were killed, the coronary perfusion pressure-flow relations were obtained during resting conditions and maximal vasodilation after a 40-second period of ischemia in beating but nonworidng isolated hearts perfused with Tyrode's solution with bovine red blood cells and albumin. In hearts from control rats, coronary autoregulation (i. I n normal hearts, coronary blood flow decreases only slightly with reduction of perfusion pressure in the autoregulatory range. 1 In the subendocardium of hypertrophied hearts with hypertension, autoregulation is impaired in the lower range of coronary perfusion pressure.2 Furthermore, coronary flow reserve estimated with adenosine, dipyridamole, or flow increases during stress or after ischemia is also decreased in hypertrophied hearts.3 -23 In previous studies, 24 -25 we reported that the maximal coronary flow rate during reactive hyperemia decreased in cardiac hypertrophy, but the decreased flow normalized after relief of pressure overload. Also, Anderson et al 26 reported that decreased flow reserve and coronary vascular structural changes in the spontaneously hypertensive rat were reversible after antihypertensive drug administration. However, there is no information concerning the reversibility of impaired coronary autoregulation in hypertrophied hearts. In the present study, we tested the hypothesis that the impaired coronary autoregulation and diminished hyperemic response to brief ischemia may reverse after relief of pressure overload. For this purpose, we used an experimental model consisting of ascending aortic banding and debanding in the rat. After isolation of the heart, we studied coronary hemodynamics in beating but nonworking hearts perfused with Tyrode's solution with bovine red blood cells and albumin because coronary autoregulation depends on myocardial metabolism.1 Moreover, because coronary flow reserve depends on coronary perfusion pressure, 118 we attempted to determine coronary flow reserve from coronary pressure-flow relations during resting conditions and during maximal vasodilation after brief ischemia. MethodsWe used male Wistar rats 6-8 weeks old. After opening the chest, we banded the ascending aorta. Four weeks after banding, we operated on the rats again for the purpose of debanding some of them. We studied coronary hemodynamics in the following

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Effect of development on coronary vasodilator reserve in the isolated guinea pig heart.

Cited by 38 publications

References 30 publications

Effect of Growth and Maturation in a Hypoxic Environment on Maximum Coronary Flow Rates of Isolated Rabbit Hearts

Effect of Growth and Maturation in a Hypoxic Environment on Maximum Coronary Flow Rates of Isolated Rabbit Hearts

Maturation of coronary responsiveness to exogenous adenosine in the rabbit

Normalization of impaired coronary circulation in hypertrophied rat hearts.

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